Selective nerve fiber stimulation for treating heart conditions

ABSTRACT

Apparatus for treating a heart condition of a subject is provided, including an electrode device, which is adapted to be coupled to a vagus nerve of the subject. A control unit is adapted to drive the electrode device to apply to the vagus nerve a stimulating current, which is capable of inducing action potentials in a therapeutic direction in a first set and a second set of nerve fibers of the vagus nerve. The control unit is also adapted to drive the electrode device to apply to the vagus nerve an inhibiting current, which is capable of inhibiting the induced action potentials traveling in the therapeutic direction in the second set of nerve fibers, the nerve fibers in the second set having generally larger diameters than the nerve fibers in the first set.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present patent application is a continuation-in-part of PCTPatent Application PCT/IL02/00068, filed Jan. 23, 2002, entitled,“Treatment of disorders by unidirectional nerve stimulation,” which is acontinuation-in-part of U.S. patent application Ser. No. 09/944,913,filed Aug. 31, 2001, entitled, “Treatment of disorders by unidirectionalnerve stimulation.” The '068 application and the '913 application areassigned to the assignee of the present patent application and areincorporated herein by reference.

[0002] This application is related to a U.S. patent application to Grosset al., filed on even date, entitled, “Electrode assembly for nervecontrol,” which is assigned to the assignee of the present patentapplication and is incorporated herein by reference.

[0003] This application claims the benefit of U.S. Provisional PatentApplication No. 60/383,157 to Ayal et al., filed May 23, 2002, entitled,“Inverse recruitment for autonomic nerve systems,” which is assigned tothe assignee of the present patent application and is incorporatedherein by reference.

FIELD OF THE INVENTION

[0004] The present invention relates generally to treating patients byapplication of electrical signals to a selected nerve or nerve bundle,and specifically to methods and apparatus for stimulating the vagusnerve for treating heart conditions.

BACKGROUND OF THE INVENTION

[0005] The use of nerve stimulation for treating and controlling avariety of medical, psychiatric, and neurological disorders has seensignificant growth over the last several decades, including fortreatment of heart conditions. In particular, stimulation of the vagusnerve (the tenth cranial nerve, and part of the parasympathetic nervoussystem) has been the subject of considerable research. The vagus nerveis composed of somatic and visceral afferents (inward conducting nervefibers, which convey impulses toward the brain) and efferents (outwardconducting nerve fibers, which convey impulses to an effector toregulate activity such as muscle contraction or glandular secretion).

[0006] The rate of the heart is restrained in part by parasympatheticstimulation from the right and left vagus nerves. When the vagus nervesfail to properly stimulate the heart, various arrhythmias may result,including tachycardia and atrial fibrillation. By artificiallystimulating the vagus nerves, it is possible to slow the heart, allowingthe heart to more completely relax and the ventricles to experienceincreased filling. With larger diastolic volumes, the heart may beatmore efficiently because it may expend less energy to overcome themyocardial viscosity and elastic forces of the heart with each beat.

[0007] Stimulation of the vagus nerve has been proposed as a method fortreating various heart conditions, including heart failure and atrialfibrillation. Heart failure is a cardiac condition characterized by adeficiency in the ability of the heart to pump blood throughout the bodyand/or to prevent blood from backing up in the lungs. Customarytreatment of heart failure includes medication and lifestyle changes. Itis often desirable to lower the heart rates of patients suffering fromfaster than normal heart rates. The effectiveness of beta blockers intreating heart disease is attributed in part to theirheart-rate-lowering effect.

[0008] Bilgutay et al., in “Vagal tuning: a new concept in the treatmentof supraventricular arrhythmias, angina pectoris, and heart failure,” J.Thoracic Cardiovas. Surg. 56(1):71-82, July, 1968, which is incorporatedherein by reference, studied the use of a permanently-implanted devicewith electrodes to stimulate the right vagus nerve for treatment ofsupraventricular arrhythmias, angina pectoris, and heart failure.Experiments were conducted to determine amplitudes, frequencies, waveshapes and pulse lengths of the stimulating current to achieve slowingof the heart rate. The authors additionally studied an external device,triggered by the R-wave of the electrocardiogram (ECG) of the subject toprovide stimulation only upon an achievement of a certain heart rate.They found that when a pulsatile current with a frequency of ten pulsesper second and 0.2 milliseconds pulse duration was applied to the vagusnerve, the heart rate could be decreased to half the resting rate whilestill preserving sinus rhythm. Low amplitude vagal stimulation wasemployed to control induced tachycardias and ectopic beats.

[0009] PCT Patent Publication WO 01/26729 to Terry et al., which isincorporated herein by reference, describes techniques to increasecardiac output in patients suffering from heart failure. An implantedneurostimulator stimulates the vagus nerve in order to decrease theheart rate towards a target rate within the normal range. The vagalstimulation frequency is described as being automatically adjusted untilthe heart rate of the patient reaches the target rate. An activitysensor detects physical activity of the patient and adjusts thefrequency of the stimulating pulses accordingly in order to elevate theheart rate during periods of physical activity.

[0010] The effect of vagal stimulation on heart rate and other aspectsof heart function, including the relationship between the timing ofvagal stimulation within the cardiac cycle and the induced effect onheart rate, has been studied in animals. For example, Zhang Y et al., in“Optimal ventricular rate slowing during atrial fibrillation by feedbackAV nodal-selective vagal stimulation,” Am J Physiol Heart Circ Physiol282:H1102-H1110 (2002), describe the application of selective vagalstimulation by varying the nerve stimulation intensity, in order toachieve graded slowing of heart rate. This article is incorporatedherein by reference.

[0011] The following articles and book, which are incorporated herein byreference, may be of interest:

[0012] Levy M N et al., in “Parasympathetic Control of the Heart”,Nervous Control of Vascular Function, Randall W C ed., Oxford UniversityPress (1984)

[0013] Armour J A et al. eds., Neurocardiology, Oxford University Press(1994)

[0014] Perez M G et al., “Effect of stimulating non-myelinated vagalaxon on atrio-ventricular conduction and left ventricular function inanaesthetized rabbits,” Auton Neurosco 86 (2001)

[0015] Jones, J F X et al., “Heart rate responses to selectivestimulation of cardiac vagal C fibres in anaesthetized cats, rats andrabbits,” J Physiol 489 (Pt 1):203-14 (1995)

[0016] Wallick D W et al., “Effects of ouabain and vagal stimulation onheart rate in the dog,” Cardiovasc. Res., 18(2):75-9 (1984)

[0017] Martin P J et al., “Phasic effects of repetitive vagalstimulation on atrial contraction,” Circ. Res. 52(6):657-63 (1983)

[0018] Wallick D W et al., “Effects of repetitive bursts of vagalactivity on atrioventricular junctional rate in dogs,” 237(3):H275-81(1979)

[0019] A number of patents describe techniques for treating arrhythmiasand/or ischemia by, at least in part, stimulating the vagus nerve.Arrhythmias in which the heart rate is too fast include fibrillation,flutter and tachycardia. Arrhythmia in which the heart rate is too slowis known as bradyarrhythmia. U.S. Pat. No. 5,700,282 to Zabara, which isincorporated herein by reference, describes techniques for stabilizingthe heart rhythm of a patient by detecting arrhythmias and thenelectronically stimulating the vagus and cardiac sympathetic nerves ofthe patient. The stimulation of vagus efferents directly causes theheart rate to slow down, while the stimulation of cardiac sympatheticnerve efferents causes the heart rate to quicken. Simultaneously,afferents from vagus and/or cardiac sympathetic nerves induce the brainto employ the brain's natural mechanisms of heart rhythm control.

[0020] U.S. Pat. No. 5,330,507 to Schwartz, which is incorporated hereinby reference, describes a cardiac pacemaker for preventing orinterrupting tachyarrhythmias and for applying pacing therapies tomaintain the heart rhythm of a patient within acceptable limits. Thedevice automatically stimulates the right or left vagal nerves as wellas the heart tissue in a concerted fashion dependent upon need.Continuous and/or phasic electrical pulses are applied. Phasic pulsesare applied in a specific relationship with the R-wave of the ECG of thepatient.

[0021] European Patent Application EP 0 688 577 to Holmström et al.,which is incorporated herein by reference, describes a device to treatatrial tachyarrhythmia by detecting arrhythmia and stimulating aparasympathetic nerve that innervates the heart, such as the vagusnerve.

[0022] U.S. Pat. Nos. 5,690,681 and 5,916,239 to Geddes et al., whichare incorporated herein by reference, describe closed-loop,variable-frequency, vagal-stimulation apparatus for control ofventricular rate during atrial fibrillation. The apparatus stimulatesthe left vagus nerve, and automatically and continuously adjusts thevagal stimulation frequency as a function of the difference betweenactual and desired ventricular excitation rates. In an alternativeembodiment, the apparatus automatically adjusts the vagal stimulationfrequency as a function of the difference between ventricular excitationrate and arterial pulse rate in order to eliminate or minimize pulsedeficit.

[0023] U.S. Pat. No. 5,203,326 to Collins, which is incorporated hereinby reference, describes a pacemaker which detects a cardiac abnormalityand responds with electrical stimulation of the heart combined withvagal nerve stimulation. The vagal stimulation frequency isprogressively increased in one-minute intervals, and, for the pulsedelivery rate selected, the heart rate is described as being slowed to adesired, stable level by increasing the pulse current.

[0024] U.S. Pat. No. 5,199,428 to Obel et al., which is incorporatedherein by reference, describes a cardiac pacemaker for detecting andtreating myocardial ischemia. The device automatically stimulates thevagal nervous system as well as the heart tissue in a concerted fashionin order to decrease cardiac workload and thereby protect themyocardium.

[0025] A number of patents and articles describe other methods anddevices for stimulating nerves to achieve a desired effect. Often thesetechniques include a design for an electrode or electrode cuff.

[0026] U.S. Pat. Nos. 4,608,985 to Crish et al. and 4,649,936 to Ungaret al., which are incorporated herein by reference, describe electrodecuffs for selectively blocking orthodromic action potentials passingalong a nerve trunk, in a manner intended to avoid causing nerve damage.

[0027] PCT Patent Publication WO 01/10375 to Felsen et al., which isincorporated herein by reference, describes apparatus for modifying theelectrical behavior of nervous tissue. Electrical energy is applied withan electrode to a nerve in order to selectively inhibit propagation ofan action potential.

[0028] U.S. Pat. No. 5,755,750 to Petruska et al., which is incorporatedherein by reference, describes techniques for selectively blockingdifferent size fibers of a nerve by applying direct electric currentbetween an anode and a cathode that is larger than the anode. Thecurrent applied to the electrodes blocks nerve transmission, but, asdescribed, does not activate the nerve fibers in either direction.

[0029] The following articles, which are incorporated herein byreference, may be of interest:

[0030] Ungar I J et al., “Generation of unidirectionally propagatingaction potentials using a monopolar electrode cuff,” Annals ofBiomedical Engineering, 14:437-450 (1986)

[0031] Sweeney J D et al., “An asymmetric two electrode cuff forgeneration of unidirectionally propagated action potentials,” IEEETransactions on Biomedical Engineering, vol. BME-33(6) (1986)

[0032] Sweeney J D et al., “A nerve cuff technique for selectiveexcitation of peripheral nerve trunk regions,” IEEE Transactions onBiomedical Engineering, 37(7) (1990)

[0033] Naples G G et al., “A spiral nerve cuff electrode for peripheralnerve stimulation,” by IEEE Transactions on Biomedical Engineering,35(11) (1988)

[0034] van den Honert C et al., “Generation of unidirectionallypropagated action potentials in a peripheral nerve by brief stimuli,”Science, 206:1311-1312 (1979)

[0035] van den Honert C et al., “A technique for collision block ofperipheral nerve: Single stimulus analysis,” MP-11, IEEE Trans. Biomed.Eng. 28:373-378 (1981)

[0036] van den Honert C et al., “A technique for collision block ofperipheral nerve: Frequency dependence,” MP-12, IEEE Trans. Biomed. Eng.28:379-382 (1981)

[0037] Rijkhoff N J et al., “Acute animal studies on the use of anodalblock to reduce urethral resistance in sacral root stimulation,” IEEETransactions on Rehabilitation Engineering, 2(2):92 (1994)

[0038] Mushahwar V K et al., “Muscle recruitment through electricalstimulation of the lumbo-sacral spinal cord,” IEEE Trans Rehabil Eng,8(1):22-9 (2000)

[0039] Deurloo K E et al., “Transverse tripolar stimulation ofperipheral nerve: a modelling study of spatial selectivity,” Med BiolEng Comput, 36(1):66-74 (1998)

[0040] Tarver W B et al., “Clinical experience with a helical bipolarstimulating lead,” Pace, Vol. 15, October, Part II (1992)

[0041] In physiological muscle contraction, nerve fibers are recruitedin the order of increasing size, from smaller-diameter fibers toprogressively larger-diameter fibers. In contrast, artificial electricalstimulation of nerves using standard techniques recruits fibers in alarger- to smaller-diameter order, because largerdiameter fibers have alower excitation threshold. This unnatural recruitment order causesmuscle fatigue and poor force gradation. Techniques have been exploredto mimic the natural order of recruitment when performing artificialstimulation of nerves to stimulate muscles.

[0042] Fitzpatrick et al., in “A nerve cuff design for the selectiveactivation and blocking of myelinated nerve fibers,” Ann. Conf. of theIEEE Eng. in Medicine and Biology Soc, 13(2), 906 (1991), which isincorporated herein by reference, describe a tripolar electrode used formuscle control. The electrode includes a central cathode flanked on itsopposite sides by two anodes. The central cathode generates actionpotentials in the motor nerve fiber by cathodic stimulation. One of theanodes produces a complete anodal block in one direction so that theaction potential produced by the cathode is unidirectional. The otheranode produces a selective anodal block to permit passage of the actionpotential in the opposite direction through selected motor nerve fibersto produce the desired muscle stimulation or suppression.

[0043] The following articles, which are incorporated herein byreference, may be of interest:

[0044] Rijkhoff N J et al., “Orderly recruitment of motoneurons in anacute rabbit model,” Ann. Conf. of the IEEE Eng., Medicine and BiologySoc., 20(5):2564 (1998)

[0045] Rijkhoff N J et al., “Selective stimulation of small diameternerve fibers in a mixed bundle,” Proceedings of the Annual ProjectMeeting Sensations/Neuros and Mid-Term Review Meeting on the TMR-NetworkNeuros, Apr. 21-23, 1999, pp. 20-21 (1999)

[0046] Baratta R et al., “Orderly stimulation of skeletal muscle motorunits with tripolar nerve cuff electrode,” IEEE Transactions onBiomedical Engineering, 36(8):836-43 (1989)

[0047] The following articles, which are incorporated herein byreference, describe techniques using point electrodes to selectivelyexcite peripheral nerve fibers:

[0048] Grill W M et al., “Inversion of the current-distance relationshipby transient depolarization,” IEEE Trans Biomed Eng, 44(1):1-9 (1997)

[0049] Goodall E V et al., “Position-selective activation of peripheralnerve fibers with a cuff electrode,” IEEE Trans Biomed Eng, 43(8):851-6(1996)

[0050] Veraart C et al., “Selective control of muscle activation with amultipolar nerve cuff electrode,” IEEE Trans Biomed Eng, 40(7):640-53(1993)

SUMMARY OF THE INVENTION

[0051] It is an object of some aspects of the present invention toprovide apparatus and methods for treating and controlling a medicalcondition by application of electrical signals to a selected nerve ornerve bundle.

[0052] It is also an object of some aspects of the present invention toprovide apparatus and methods for treating and controlling a medicalcondition by application of electrical signals to a selected nerve ornerve bundle while minimizing adverse side effects.

[0053] It is a further object of some aspects of the present inventionto provide apparatus and methods for treating and controlling heartconditions by application of electrical signals to the vagus nerve,while minimizing adverse side effects.

[0054] It is still a further object of some aspects of the presentinvention to provide apparatus and methods for treating and controllingheart failure by reducing the heart rate and/or cardiac contractility.

[0055] It is yet a further object of some aspects of the presentinvention to provide apparatus and methods for treating and controllingheart failure by slowing the heart rate without inducing excessivevariability in the induced heart rate.

[0056] It is an additional object of some aspects of the presentinvention to provide apparatus and methods for treating and controllingheart arrhythmias, such as fibrillation, atrial fibrillation ortachycardia, by slowing and/or stabilizing the heart rate, and/orreducing cardiac contractility.

[0057] It is yet an additional object of some aspects of the presentinvention to provide apparatus and methods for treating and controllingheart arrhythmias without inducing excessive variability in the inducedheart rate.

[0058] It is still an additional object of some aspects of the presentinvention to provide apparatus and methods for treating and controllingheart conditions without the systemic side effects sometimes caused bypharmaceutical treatments of heart conditions.

[0059] In preferred embodiments of the present invention, apparatus fortreating a heart condition comprises a multipolar electrode device thatis applied to a portion of a vagus nerve that innervates the heart of apatient. Typically, the system is configured to treat heart failureand/or heart arrhythmia, such as atrial fibrillation or tachycardia. Acontrol unit preferably drives the electrode device to (i) apply signalsto induce the propagation of efferent action potentials towards theheart, and (ii) suppress artificially-induced afferent action potentialstowards the brain, in order to minimize any unintended side effect ofthe signal application.

[0060] When inducing efferent action potentials towards the heart, thecontrol unit preferably drives the electrode device to selectivelyrecruit nerve fibers beginning with smaller-diameter fibers, and torecruit progressively larger-diameter fibers as the desired stimulationlevel increases. Preferably, in order to achieve this smallert-to-largerdiameter fiber recruitment order, the control unit stimulates fibersessentially of all diameters using cathodic current from a centralcathode, while simultaneously inhibiting fibers in a larger-to-smallerdiameter order using anodal current (“efferent anodal current”) from aset of one or more anodes placed between the central cathode and theedge of the electrode device closer to the heart (“the efferent anodeset”). The amount of parasympathetic stimulation delivered to the heartis preferably increased by decreasing the number of fibers affected bythe efferent anodal current, in a smaller-to-larger diameter order,e.g., by decreasing the amplitude or frequency of the efferent anodalcurrent applied to the nerve.

[0061] The control unit preferably suppresses afferent action potentialsinduced by the cathodic current by inhibiting essentially all or a largefraction of fibers using anodal current (“afferent anodal current”) froma second set of one or more anodes (the “afferent anode set”). Theafferent anode set is preferably placed between the central cathode andthe edge of the electrode device closer to the brain (the “afferentedge”), to block essentially all fibers from conveying signals in thedirection of the brain during application of the afferent anodalcurrent.

[0062] In some preferred embodiments of the present invention, theefferent anode set comprises a plurality of anodes. Application of theefferent anodal current in appropriate ratios from the plurality ofanodes in these embodiments generally minimizes the “virtual cathodeeffect,” whereby application of too large an anodal current creates avirtual cathode, which stimulates rather than blocks fibers. When suchtechniques are not used, the virtual cathode effect generally hindersblocking of smaller-diameter fibers, because a relatively large anodalcurrent is typically necessary to block such fibers, and this same largeanodal current induces the virtual cathode effect. Likewise, theafferent anode set preferably comprises a plurality of anodes in orderto minimize the virtual cathode effect in the direction of the brain.

[0063] Preferably, parasympathetic stimulation of the vagus nerve isapplied responsive to one or more sensed physiological parameters orother parameters, such as heart rate, electrocardiogram (ECG), bloodpressure, indicators of cardiac contractility, cardiac output,norepinephrine concentration, or motion of the patient. Preferably,stimulation is applied in a closed-loop system in order to achieve andmaintain a desired heart rate responsive to one or more such sensedparameters.

[0064] In some preferred embodiments of the present invention, vagalstimulation is applied in a series of pulses. The application of theseries of pulses in each cardiac cycle preferably commences after avariable delay after a detected R-wave, P-wave, or other feature of anECG. The delay is preferably calculated in real time using a function,the inputs of which include one or more pre-programmed but updateableconstants and one or more sensed parameters, such as the R-R intervalbetween cardiac cycles and/or the P-R interval. Alternatively oradditionally, a lookup table of delays is used to determine in real timethe appropriate delay for each application of pulses, based on the oneor more sensed parameters.

[0065] Advantageously, the techniques described herein generally enablerelatively fine control of the level of stimulation of the vagus nerve,by imitating the natural physiological smaller-to-larger diameterrecruitment order of nerve fibers. This recruitment order allowsimproved and more natural control over the heart rate. Such fine controlis particularly advantageous when applied in a closed-loop system,wherein such control results in smaller changes in heart rate and lowerlatencies in the control loop, which generally contribute to greaterloop stability and reduced loop stabilization time. The use of avariable delay prior to application of pulses generally reduces thebeat-to-beat variability of the heart rate sometimes experienced whenusing techniques having a constant ECG-based delay before application ofpulses.

[0066] “Vagus nerve,” and derivatives thereof, as used in thespecification and the claims, is to be understood to include portions ofthe left vagus nerve, the right vagus nerve, and branches of the vagusnerve such as the superior cardiac nerve. Similarly, stimulation of thevagus nerve is described herein by way of illustration and notlimitation, and it is to be understood that stimulation of otherautonomic nerves, including nerves in the epicardial fat pads, fortreatment of heart conditions or other conditions, is also includedwithin the scope of the present invention.

[0067] “Heart failure,” as used in the specification and the claims, isto be understood to include all forms of heart failure, includingischemic heart failure, nonischemic heart failure, and diastolic heartfailure.

[0068] There is therefore provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a heartcondition of a subject, including:

[0069] an electrode device, adapted to be coupled to a vagus nerve ofthe subject; and

[0070] a control unit, adapted to:

[0071] drive the electrode device to apply to the vagus nerve astimulating current, which is capable of inducing action potentials in atherapeutic direction in a first set and a second set of nerve fibers ofthe vagus nerve, and

[0072] drive the electrode device to apply to the vagus nerve aninhibiting current, which is capable of inhibiting the induced actionpotentials traveling in the therapeutic direction in the second set ofnerve fibers, the nerve fibers in the second set having generally largerdiameters than the nerve fibers in the first set.

[0073] Preferably, the therapeutic direction is an efferent therapeuticdirection towards a heart of the subject. Alternatively or additionally,the therapeutic direction is an afferent therapeutic direction towards abrain of the subject.

[0074] In a preferred embodiment, the control unit increases a number ofaction potentials traveling in the therapeutic direction by decreasingan amplitude of the applied inhibiting current, and/or decreases anumber of action potentials traveling in the therapeutic direction byincreasing an amplitude of the applied inhibiting current.

[0075] In a preferred embodiment, the heart condition includes heartfailure and/or cardiac arrhythmia, and the apparatus is adapted to treatthe heart condition.

[0076] Optionally, the apparatus includes an override, adapted to beused by the subject so as to influence the application by the electrodedevice of the stimulating and inhibiting currents.

[0077] In a preferred embodiment, the apparatus includes a pacemaker,and the control unit is adapted to drive the pacemaker to apply pacingpulses to a heart of the subject. Alternatively, the apparatus includesan implantable cardioverter defibrillator (ICD), and the control unit isadapted to drive the ICD to apply energy to a heart of the subject.

[0078] Preferably, the control unit is adapted to drive the electrodedevice to apply the stimulating current and/or the inhibiting current ina series of pulses.

[0079] In a preferred embodiment, the control unit receives anelectrical signal from the electrode device, and drives the electrodedevice to regulate the stimulating and/or inhibiting current responsiveto the electrical signal.

[0080] Preferably, the electrode device includes a cathode, adapted toapply the stimulating current, and a primary set of anodes, whichapplies the inhibiting current. Most preferably, the primary set ofanodes includes a primary anode and a secondary anode, disposed so thatthe primary anode is located between the secondary anode and thecathode, and the secondary anode applies a current with an amplitudeless than about one half an amplitude of a current applied by theprimary anode.

[0081] Preferably, the control unit is adapted to drive the electrodedevice to apply the stimulating current so as to regulate a heart rateof the subject. Most preferably, the control unit is adapted to drivethe electrode device to regulate an amplitude of the stimulating currentso as to regulate the heart rate of the subject.

[0082] Alternatively or additionally, the control unit drives theelectrode device to apply the inhibiting current so as to regulate aheart rate of the subject. In this case, the control unit preferablydrives the electrode device to regulate an amplitude of the inhibitingcurrent so as to regulate the heart rate of the subject.

[0083] Preferably, the control unit is adapted to drive the electrodedevice to apply the stimulating and inhibiting currents in a series ofpulses. Most preferably, the control unit:

[0084] drives the electrode device to apply the stimulating andinhibiting currents in a series of about one to 20 pulses,

[0085] configures the pulses to have a duration of between about one andthree milliseconds, and/or

[0086] drives the electrode device to apply the stimulating andinhibiting currents in the series of pulses over a period of betweenabout one and about 200 milliseconds.

[0087] Preferably, the control unit drives the electrode device to applythe stimulating and inhibiting currents in the series of pulses so as toregulate a heart rate of the subject. Most preferably, the control unitregulates the number of pulses in the series of pulses so as to regulatethe heart rate of the subject. Optionally, the control unit regulates aduration of each pulse so as to regulate the heart rate of the subject.Optionally, the control unit varies a length of a period of applicationof the series of pulses so as to regulate the heart rate of the subject.

[0088] In a preferred embodiment, the control unit drives the electrodedevice to apply to the vagus nerve a second inhibiting current, which iscapable of inhibiting device-induced action potentials traveling in anon-therapeutic direction opposite the therapeutic direction in thefirst and second sets of nerve fibers.

[0089] Preferably, the control unit to drives the electrode device toapply the second inhibiting current to the vagus nerve at a primary anda secondary location, the primary location located between the secondarylocation and an application location of the stimulating current, and toapply at the secondary location a current with an amplitude less thanabout one half an amplitude of a current applied at the primarylocation.

[0090] In a preferred embodiment, the apparatus includes a sensor unit,and the control unit is adapted to receive at least one sensed parameterfrom the sensor unit, and to drive the electrode device to apply thestimulating and inhibiting currents responsive to the at least onesensed parameter.

[0091] Preferably, the control unit is adapted to determine a targetheart rate of the subject responsive to the at least one sensedparameter, and the control unit is adapted to drive the electrode deviceto apply the stimulating and inhibiting currents so as to adjust a heartrate of the subject towards the target heart rate.

[0092] The sensor unit may include one or more of the following sensors,in which case the control unit receives the at least one sensedparameter from the following one or more sensors:

[0093] a blood pressure sensor,

[0094] a left ventricular pressure (LVP) sensor,

[0095] an accelerometer (in which case, the at least one sensedparameter includes motion of the subject),

[0096] a detector of norepinephrine concentration in the subject, and/or

[0097] an impedance cardiography sensor.

[0098] Alternatively or additionally, the at least one sensed parameterincludes an indicator of decreased cardiac contractility, an indicatorof cardiac output, and/or an indicator of a time derivative of a LVP,and the control unit receives the indicator.

[0099] In a preferred embodiment, the sensor unit includes anelectrocardiogram (ECG) monitor, the at least one sensed parameterincludes an ECG value, and the control unit receives the at least onesensed parameter from the ECG monitor.

[0100] Preferably, the at least one sensed parameter includes an ECGreading indicative of a presence of arrhythmia, and the control unit isadapted to receive the at least one sensed parameter from the ECGmonitor. Optionally, the at least one sensed parameter includes anindication of a heart rate of the subject, and the control unit isadapted to receive the indication of the heart rate. Further optionally,the at least one sensed parameter includes indications of a plurality ofheart rates of the subject at a respective plurality of points in time,and the control unit is adapted to receive the at least one sensedparameter and to determine a measure of variability of heart rateresponsive thereto.

[0101] In a preferred embodiment, the sensor unit is adapted to sense aninitiation physiological parameter and a termination physiologicalparameter of the subject, and the control unit is adapted to drive theelectrode device to apply the stimulating and inhibiting currents to thevagus nerve after a delay, to initiate the delay responsive to thesensing of the initiation physiological parameter, and to set a lengthof the delay responsive to the termination physiological parameter.

[0102] Preferably, the control unit is adapted to determine a targetheart rate of the subject responsive to the at least one sensedparameter, and the control unit is adapted to set the delay so as toadjust the heart rate towards the target heart rate.

[0103] Optionally, the termination physiological parameter includes anatrioventricular (AV) delay of the subject, and the control unit isadapted to set the length of the delay responsive to the AV delay.

[0104] Preferably, the sensor unit includes an electrocardiogram (ECG)monitor, and the initiation physiological parameter includes a P-wave orR-wave of a cardiac cycle of the subject, and wherein the control unitis adapted to initiate the delay responsive to the sensing of the P-waveor R-wave, as the case may be. Preferably, the termination physiologicalparameter includes a difference in time between two features of an ECGsignal recorded by the ECG monitor, such as an R-R interval between asensing of an R-wave of a first cardiac cycle of the subject and asensing of an R-wave of a next cardiac cycle of the subject, or a P-Rinterval between a sensing of a P-wave of a cardiac cycle of the subjectand a sensing of an R-wave of the cardiac cycle, and the control unitsets the length of the delay responsive to the termination physiologicalparameter.

[0105] There is further provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a heartcondition of a subject, including:

[0106] a cathode, adapted to apply to a vagus nerve of the subject astimulating current which is capable of inducing action potentials inthe vagus nerve; and

[0107] a primary and a secondary anode, adapted to be disposed so thatthe primary anode is located between the secondary anode and thecathode, and adapted to apply to the vagus nerve respective primary andsecondary inhibiting currents which are capable of inhibiting actionpotentials in the vagus nerve.

[0108] Preferably, the primary and secondary anodes are adapted to beplaced between about 0.5 and about 2.0 millimeters apart from oneanother. Further preferably, the secondary anode is adapted to apply thesecondary inhibiting current with an amplitude equal to between about 2and about 5 milliamps. Still further preferably, the secondary anode isadapted to apply the secondary inhibiting current with an amplitude lessthan about one half an amplitude of the primary inhibiting currentapplied by the primary anode.

[0109] In a preferred embodiment, the primary anode, the secondaryanode, and/or the cathode includes a ring electrode adapted to apply agenerally uniform current around a circumference of the vagus nerve.Alternatively or additionally, the primary anode, the secondary anode,and/or the cathode includes a plurality of discrete primary anodes,adapted to be disposed at respective positions around an axis of thevagus nerve.

[0110] Optionally, the apparatus includes a tertiary anode, adapted tobe disposed such that the secondary anode is between the tertiary anodeand the primary anode.

[0111] Preferably, the electrode device includes an efferent edge, andthe cathode is adapted to be disposed closer than the anodes to theefferent edge of the electrode device.

[0112] Preferably, the cathode and/or the anodes are adapted to applythe stimulating current so as to regulate a heart rate of the subject.

[0113] Optionally, the cathode includes a plurality of discretecathodes, adapted to be disposed at respective positions around an axisof the vagus nerve, so as to selectively stimulate nerve fibers of thevagus nerve responsive to the positions of the nerve fibers in the vagusnerve.

[0114] Optionally, the apparatus includes a set of one or more blockinganodes, adapted to be disposed such that the cathode is between the setof blocking anodes and the primary anode, and adapted to apply to thevagus nerve a current which is capable of inhibiting action potentialspropagating in the vagus nerve in a direction from the cathode towardsthe set of blocking anodes.

[0115] Preferably, the set of blocking anodes includes a first anode anda second anode, adapted to be disposed such that the first anode islocated between the second anode and the cathode, and wherein the secondanode is adapted to apply a current with an amplitude less than aboutone half an amplitude of a current applied by the first anode.

[0116] Preferably, the electrode device includes an afferent edge,wherein the cathode is adapted to be disposed closer than the anodes tothe afferent edge of the electrode device.

[0117] Preferably, the apparatus includes a cuff, and anelectrically-insulating element coupled to an inner portion of the cuff,and the primary anode and the cathode are adapted to be mounted in thecuff and separated from one another by the insulating element.Preferably, the primary and secondary anodes and the cathode arerecessed in the cuff so as not to be in direct contact with the vagusnerve.

[0118] Preferably, the apparatus includes a control unit, adapted todrive the cathode and the anodes to apply the respective currents to thevagus nerve, so as to treat the subject.

[0119] Preferably, the cathode is adapted to apply the stimulatingcurrent and the anodes are adapted to apply the inhibiting current so asto regulate a heart rate of the subject. Optionally, the cathode isadapted to vary an amplitude of the applied stimulating current and theanodes are adapted to vary an amplitude of the applied inhibitingcurrent so as to regulate a heart rate of the subject.

[0120] There is still further provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a heartcondition of a subject, including:

[0121] an electrode device, adapted to be coupled to a vagus nerve ofthe subject;

[0122] a sensor unit, adapted to sense an initiation physiologicalparameter and a termination physiological parameter of the subject; and

[0123] a control unit, adapted to:

[0124] drive the electrode device to apply to the vagus nerve, after adelay, a current which is capable of inducing action potentials thatpropagate in the vagus nerve,

[0125] initiate the delay responsive to the sensing of the initiationphysiological parameter, and

[0126] set a length of the delay responsive to the terminationphysiological parameter.

[0127] Optionally, the sensor unit includes a single sensor, adapted tosense the initiation physiological parameter and the terminationphysiological parameter.

[0128] The termination physiological parameter may include anatrioventricular (AV) delay of the subject, a respiration parameter ofthe subject, and the control unit is adapted to set the length of thedelay responsive to the termination physiological parameter.

[0129] Preferably, the control unit is adapted to:

[0130] drive the electrode device to apply to the vagus nerve astimulating current, which is capable of inducing action potentials in atherapeutic direction in a first set and a second set of nerve fibers ofthe vagus nerve, and

[0131] drive the electrode device to apply to the vagus nerve aninhibiting current, which is capable of inhibiting the induced actionpotentials traveling in the therapeutic direction in the second set ofnerve fibers, the nerve fibers in the second set having generally largerdiameters than the nerve fibers in the first set.

[0132] Optionally, the termination physiological parameter includes ablood pressure of the subject, and wherein the control unit is adaptedto set the length of the delay responsive to the blood pressure.

[0133] Preferably, the sensor unit is adapted to sense a rate-settingparameter of the subject, wherein the rate-setting parameter includes ablood pressure of the subject, and wherein the control unit is adaptedto receive the rate-setting parameter from the sensor unit and to drivethe electrode device to apply the current responsive to the rate-settingparameter.

[0134] Optionally, the rate-setting parameter includes the initiationphysiological parameter and/or the termination physiological parameter,and the control unit is adapted to drive the electrode device to applythe current responsive to the initiation physiological parameter so asto regulate the heart rate of the subject.

[0135] Preferably, the control unit is adapted to set the length of thedelay so as to adjust the heart rate towards the target heart rate.Optionally, the control unit is adapted to access a lookup table ofdelays, and to set the length of the delay using the lookup table andresponsive to the initiation and termination physiological parameters.

[0136] Preferably, the initiation physiological parameter includes aP-wave, R-wave, Q-wave, S-wave, or T-wave of a cardiac cycle of thesubject, and wherein the control unit is adapted to initiate the delayresponsive to the sensing of the cardiac wave.

[0137] Preferably, the termination physiological parameter includes adifference in time between two features of an ECG signal recorded by theECG monitor, and the control unit is adapted to set the length of thedelay responsive to the difference in time between the two features. Thetermination physiological parameter may include an R-R interval betweena sensing of an R-wave of a first cardiac cycle of the subject and asensing of an R-wave of a next cardiac cycle of the subject, and whereinthe control unit is adapted to set the length of the delay responsive tothe R-R interval. Alternatively or additionally, the terminationphysiological parameter includes an average of R-R intervals sensed fora number of cardiac cycles, and wherein the control unit is adapted toset the length of the delay responsive to the average of the R-Rintervals.

[0138] Alternatively, the termination physiological parameter includes aP-R interval between a sensing of a P-wave of a cardiac cycle of thesubject and a sensing of an R-wave of the cardiac cycle, and wherein thecontrol unit is adapted to set the length of the delay responsive to theP-R interval. Alternatively or additionally, the terminationphysiological parameter includes an average of P-R intervals sensed fora number of cardiac cycles, and wherein the control unit is adapted toset the length of the delay responsive to the average of the P-Rintervals.

[0139] There is also provided, in accordance with a preferred embodimentof the present invention, apparatus for treating a condition of asubject, including:

[0140] an electrode device, adapted to be coupled to an autonomic nerveof the subject; and

[0141] a control unit, adapted to:

[0142] drive the electrode device to apply to the nerve a stimulatingcurrent, which is capable of inducing action potentials in a therapeuticdirection in a first set and a second set of nerve fibers of the nerve,and

[0143] drive the electrode device to apply to the nerve an inhibitingcurrent, which is capable of inhibiting the induced action potentialstraveling in the therapeutic direction in the second set of nervefibers, the nerve fibers in the second set having generally largerdiameters than the nerve fibers in the first set.

[0144] Preferably, the autonomic nerve includes one or more of thefollowing:

[0145] a lacrimal nerve,

[0146] a salivary nerve,

[0147] a vagus nerve,

[0148] a pelvic splanchnic nerve,

[0149] a sympathetic nerve,

[0150] and the control unit is adapted to drive the electrode device toapply the stimulating and inhibiting currents to the nerve.

[0151] Preferably, the control unit is adapted to drive the electrodedevice to apply the stimulating and inhibiting currents to the nerve soas to affect behavior of one of the following, so as to treat thecondition:

[0152] a lung of the subject,

[0153] a stomach of the subject,

[0154] a pancreas of the subject,

[0155] a small intestine of the subject,

[0156] a liver of the subject,

[0157] a spleen of the subject,

[0158] a kidney of the subject,

[0159] a bladder of the subject,

[0160] a rectum of the subject,

[0161] a large intestine of the subject,

[0162] a reproductive organ of the subject, and/or

[0163] an adrenal gland of the subject.

[0164] There is additionally provided, in accordance with a preferredembodiment of the present invention, apparatus for treating a conditionof a subject, including:

[0165] a cathode, adapted to apply to an autonomic nerve of the subjecta stimulating current which is capable of inducing action potentials inthe nerve; and

[0166] a primary and a secondary anode, adapted to be disposed so thatthe primary anode is located between the secondary anode and thecathode, and adapted to apply to the nerve respective primary andsecondary inhibiting currents which are capable of inhibiting actionpotentials in the nerve.

[0167] There is yet additionally provided, in accordance with apreferred embodiment of the present invention, a method for treating aheart condition of a subject, including:

[0168] applying, to a vagus nerve of the subject, a stimulating currentwhich is capable of inducing action potentials in a therapeuticdirection in a first set and a second set of nerve fibers of the vagusnerve; and

[0169] applying to the vagus nerve an inhibiting current which iscapable of inhibiting the induced action potentials traveling in thetherapeutic direction in the second set of nerve fibers, the nervefibers in the second set having generally larger diameters than thenerve fibers in the first set.

[0170] There is still additionally provided, in accordance with apreferred embodiment of the present invention, a method for treating aheart condition of a subject, including:

[0171] applying, to a vagus nerve of the subject, at a stimulationlocation, a stimulating current which is capable of inducing actionpotentials in the vagus nerve, so as to treat the subject; and

[0172] applying to the vagus nerve at a primary and a secondarylocation, the primary location located between the secondary locationand the stimulation location, an inhibiting current which is capable ofinhibiting action potentials in the vagus nerve.

[0173] There is further provided, in accordance with a preferredembodiment of the present invention, a method for treating a heartcondition of a subject, including:

[0174] sensing an initiation physiological parameter and a terminationphysiological parameter of the subject;

[0175] setting a length of a delay period responsive to the terminationphysiological parameter;

[0176] initiating the delay period responsive to the initiationparameter; and

[0177] upon completion of the delay period, applying, to a vagus nerveof the subject, a current which is capable of inducing action potentialsthat propagate in the vagus nerve.

[0178] There is still further provided, in accordance with a preferredembodiment of the present invention, a method for treating a conditionof a subject, including:

[0179] applying, to an autonomic nerve of the subject, a stimulatingcurrent which is capable of inducing action potentials in a therapeuticdirection in a first set and a second set of nerve fibers of the nerve;and

[0180] applying to the nerve an inhibiting current which is capable ofinhibiting the induced action potentials traveling in the therapeuticdirection in the second set of nerve fibers, the nerve fibers in thesecond set having generally larger diameters than the nerve fibers inthe first set.

[0181] There is also provided, in accordance with a preferred embodimentof the present invention, a method for treating a condition of asubject, including:

[0182] applying, to an autonomic nerve of the subject, at a stimulationlocation, a stimulating current which is capable of inducing actionpotentials in the nerve, so as to treat the subject; and

[0183] applying to the nerve at a primary and a secondary location, theprimary location located between the secondary location and thestimulation location, an inhibiting current which is capable ofinhibiting action potentials in the nerve.

[0184] The present invention will be more fully understood from thefollowing detailed description of a preferred embodiment thereof, takentogether with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

[0185]FIG. 1 is a block diagram that schematically illustrates a vagalstimulation system applied to a vagus nerve of a patient, in accordancewith a preferred embodiment of the present invention;

[0186]FIG. 2A is a simplified cross-sectional illustration of amultipolar electrode device applied to a vagus nerve, in accordance witha preferred embodiment of the present invention;

[0187]FIG. 2B is a simplified perspective illustration of the electrodedevice of FIG. 2A;

[0188]FIG. 3 is a simplified perspective illustration of a multipolarpoint electrode device applied to a vagus nerve, in accordance with apreferred embodiment of the present invention;

[0189]FIG. 4 is a conceptual illustration of the application of currentto a vagus nerve, in accordance with a preferred embodiment of thepresent invention; and

[0190]FIG. 5 is a simplified illustration of an electrocardiogram (ECG)recording and of example timelines showing the timing of the applicationof a series of stimulation pulses, in accordance with a preferredembodiment of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0191]FIG. 1 is a block diagram that schematically illustrates a vagalstimulation system 18 comprising a multipolar electrode device 40, inaccordance with a preferred embodiment of the present invention.Electrode device 40 is applied to a portion of a vagus nerve 36 thatinnervates a heart 30 of a patient. Typically, system 18 is utilized fortreating a heart condition such as heart failure and/or cardiacarrhythmia. Vagal stimulation system 18 further comprises an implantedor external control unit 20, which typically communicates with electrodedevice 40 over a set of leads 42. Control unit 20 drives electrodedevice 40 to (i) apply signals to induce the propagation of efferentnerve impulses towards heart 30, and (ii) suppress artificially-inducedafferent nerve impulses towards a brain 34 of the patient, in order tominimize unintended side effects of the signal application. The efferentnerve pulses in vagus nerve 36 are induced by electrode device 40 inorder to regulate the heart rate of the patient.

[0192] For some applications, control unit 20 is adapted to receivefeedback from one or more of the electrodes in electrode device 40, andto regulate the signals applied to the electrode device responsivethereto. For example, control unit 20 may analyze latencies of variouspeaks in a compound action potential (CAP) signal recorded by theelectrodes, in order to determine a relative proportion of stimulatedlarger fibers (having faster conduction velocities) to smaller fibers(having slower conduction velocities). Alternatively or additionally,control unit 20 analyzes an area of the CAP, in order to determine anoverall effect of the stimulation. Preferably, a relationship isdetermined between the effect on heart rate and the recorded CAP areaand/or CAP latencies, and this relationship is used by the control unitto modulate the steps described in (i) and (ii) above. In a preferredembodiment, the feedback is received by electrodes other than those usedto apply signals to the nerve.

[0193] Control unit 20 is preferably adapted to receive and analyze oneor more sensed physiological parameters or other parameters of thepatient, such as heart rate, electrocardiogram (ECG), blood pressure,indicators of decreased cardiac contractility, cardiac output,norepinephrine concentration, or motion of the patient. In order toreceive these sensed parameters, control unit 20 may comprise, forexample, an ECG monitor 24, connected to a site on the patient's bodysuch as a heart 30, and/or the control unit may comprise anaccelerometer 22 for detecting motion of the patient. Alternatively, ECGmonitor 24 and/or accelerometer 22 comprise separate implanted devicesplaced external to control unit 20, and, optionally, external to thepatient's body. Alternatively or additionally, control unit 20 receivessignals from one or more physiological sensors 26, such as bloodpressure sensors. Sensors 26 are preferably implanted in the patient,for example in a left ventricle 32 of heart 30. In a preferredembodiment, control unit 20 comprises or is coupled to an implanteddevice 25 for monitoring and correcting the heart rate, such as animplantable cardioverter defibrillator (ICD) or a pacemaker (e.g., abi-ventricular or standard pacemaker). For example, implanted device 25may be incorporated into a control loop executed by control unit 20, inorder to increase the heart rate when the heart rate for any reason istoo low.

[0194]FIG. 2A is a simplified cross-sectional illustration of agenerally-cylindrical electrode device 40 applied to vagus nerve 36, inaccordance with a preferred embodiment of the present invention.Electrode device 40 comprises a central cathode 46 for applying anegative current (“cathodic current”) in order to stimulate vagus nerve36, as described below. Electrode device 40 additionally comprises a setof one or more anodes 44 (44 a, 44 b, herein: “efferent anode set 44”),placed between cathode 46 and the edge of electrode device 40 closer toheart 30 (the “efferent edge”). Efferent anode set 44 applies a positivecurrent (“efferent anodal current”) to vagus nerve 36, for blockingaction potential conduction in vagus nerve 36 induced by the cathodiccurrent, as described below. Preferably, electrode device 40 comprisesan additional set of one or more anodes 45 (45 a, 45 b, herein:“afferent anode set 45”), placed between cathode 46 and the edge ofelectrode device 40 closer to brain 34. Afferent anode set 45 applies apositive current (“afferent anodal current”) to vagus nerve 36, in orderto block propagation of action potentials in the direction of the brainduring application of the cathodic current.

[0195] Cathodes 46 and anode sets 44 and 45 (collectively, “electrodes”)are preferably mounted in an electrically-insulating cuff 48 andseparated from one another by insulating elements such as protrusions 49of the cuff. Preferably, the width of the electrodes is between about0.5 and about 1 millimeter, or is equal to approximately one-half theradius of the vagus nerve. Further preferably, in order to achievegenerally uniform field distributions of the currents generated by theelectrodes, the electrodes are recessed so as not to come in directcontact with vagus nerve 36. Most preferably, the distance between theelectrodes and the axis of the vagus nerve is between about 1.5 and 4millimeters, and is greater than the closest distance from the ends ofthe protrusions to the axis of the vagus nerve. Preferably, protrusions49 are relatively short (as shown). Most preferably, the distancebetween the ends of protrusions 49 and the center of the vagus nerve isbetween about 1.5 and 3 millimeters. (Generally, the radius of the vagusnerve is between about 1 and 2 millimeters.) Alternatively, for someapplications, protrusions 49 are longer and/or the electrodes are placedcloser to the vagus nerve in order to reduce the energy consumption ofelectrode device 40.

[0196] In a preferred embodiment of the present invention, efferentanode set 44 comprises a plurality of anodes 44, typically two anodes 44a and 44 b, spaced approximately 0.5 to 2.0 millimeters apart.Application of the efferent anodal current in appropriate ratios from aplurality of anodes generally minimizes the “virtual cathode effect,”whereby application of too large an anodal current stimulates ratherthan blocks fibers. In a preferred embodiment, anode 44 a applies acurrent with an amplitude equal to about 2 to about 5 milliamps(typically one-third) of the amplitude of the current applied by anode44 b. When such techniques are not used, the virtual cathode effectgenerally hinders blocking of smaller-diameter fibers, as describedbelow, because a relatively large anodal current is generally necessaryto block such fibers.

[0197] Anode 44 a is preferably positioned in cuff 48 to apply currentat the location on vagus nerve 36 where the virtual cathode effect ismaximally generated by anode 44 b. For applications in which theblocking current through anode 44 b is expected to vary substantially,efferent anode set 44 preferably comprises a plurality ofvirtual-cathode-inhibiting anodes 44 a, one or more of which isactivated at any time based on the expected magnitude and location ofthe virtual cathode effect.

[0198] Likewise, afferent anode set 45 preferably comprises a pluralityof anodes 45, typically two anodes 45 a and 45 b, in order to minimizethe virtual cathode effect in the direction of the brain. In certainelectrode configurations, cathode 46 comprises a plurality of cathodesin order to minimize the “virtual anode effect,” which is analogous tothe virtual cathode effect.

[0199] As appropriate, techniques described herein are practiced inconjunction with methods and apparatus described in the above-cited U.S.patent application to Gross et al., filed on even date with the presentpatent application, entitled, “Electrode assembly for nerve control,”which is assigned to the assignee of the present patent application andis incorporated herein by reference. Alternatively or additionally,techniques described herein are practiced in conjunction with methodsand apparatus described in U.S. Provisional Patent Application No.60/383,157 to Ayal et al., filed May 23, 2002, entitled, “Inverserecruitment for autonomic nerve systems,” which is assigned to theassignee of the present patent application and is incorporated herein byreference.

[0200]FIG. 2B is a simplified perspective illustration of electrodedevice 40. When applied to vagus nerve 36, electrode device 40preferably encompasses the nerve. As described, control unit 20typically drives electrode device 40 to (i) apply signals to vagus nerve36 in order to induce the propagation of efferent action potentialstowards heart 30, and (ii) suppress artificially-induced afferent actionpotentials towards brain 34. The electrodes preferably comprise ringelectrodes adapted to apply a generally uniform current around thecircumference of the nerve, as best shown in FIG. 2B.

[0201]FIG. 3 is a simplified perspective illustration of a multipolarpoint electrode device 140 applied to vagus nerve 36, in accordance witha preferred embodiment of the present invention. In this embodiment,anodes 144 a and 144 b and a cathode 146 preferably comprise pointelectrodes (typically 2 to 100), fixed to an insulating cuff 148 andarranged around vagus nerve 36 so as to selectively stimulate nervefibers according to their positions inside the nerve. In this case,techniques described in the above-cited articles by Grill et al.,Goodall et al., and/or Veraart et al. are preferably used. The pointelectrodes preferably have a surface area between about 0.01 mm2 and 1mm2. In some applications, the point electrodes are in contact withvagus nerve 36, as shown, while in other applications the pointelectrodes are recessed in cuff 148, so as not to come in direct contactwith vagus nerve 36, similar to the recessed ring electrode arrangementdescribed above with reference to FIG. 2A. For some applications, one ormore of the electrodes, such as cathode 146 or anode 144 a, comprise aring electrode, as described with reference to FIG. 2B, such thatelectrode device 140 comprises both ring electrode(s) and pointelectrodes. Additionally, electrode device 40 optionally comprises anafferent anode set (positioned like anodes 45 a and 45 b in FIG. 2A),the anodes of which comprise point electrodes and/or ring electrodes.

[0202] Alternatively, ordinary, non-cuff electrodes are used, such aswhen the electrodes are placed on the epicardial fat pads instead of onthe vagus nerve.

[0203]FIG. 4 is a conceptual illustration of the application of currentto vagus nerve 36 in order to achieve smaller-to-larger diameter fiberrecruitment, in accordance with a preferred embodiment of the presentinvention. When inducing efferent action potentials towards heart 30,control unit 20 drives electrode device 40 to selectively recruit nervefibers beginning with smaller-diameter fibers and to progressivelyrecruit larger-diameter fibers as the desired stimulation levelincreases. This smaller-to-larger diameter recruitment order mimics thebody's natural order of recruitment.

[0204] Preferably, in order to achieve this recruitment order, thecontrol unit stimulates fibers essentially of all diameters usingcathodic current from cathode 46, while simultaneously inhibiting fibersin a larger-to-smaller diameter order using efferent anodal current fromefferent anode set 44. For example, FIG. 4 illustrates the recruitmentof a single, smallest nerve fiber 56, without the recruitment of anylarger fibers 50, 52 and 54. The depolarizations generated by cathode 46stimulate all of the nerve fibers shown, producing action potentials inboth directions along all the nerve fibers. Efferent anode set 44generates a hyperpolarization effect sufficiently strong to block onlythe three largest nerve fibers 50, 52 and 54, but not fiber 56. Thisblocking order of larger-to-smaller diameter fibers is achieved becauselarger nerve fibers are inhibited by weaker anodal currents than aresmaller nerve fibers. Stronger anodal currents inhibit progressivelysmaller nerve fibers. When the action potentials induced by cathode 46in larger fibers 50, 52 and 54 reach the hyperpolarized region in thelarger fibers adjacent to efferent anode set 44, these action potentialsare blocked. On the other hand, the action potentials induced by cathode46 in smallest fiber 56 are not blocked, and continue travelingunimpeded toward heart 30. Anode pole 44 a is shown generating lesscurrent than anode pole 44 b in order to minimize the virtual cathodeeffect in the direction of the heart, as described above.

[0205] When desired, in order to increase the parasympatheticstimulation delivered to the heart, the number of fibers not blocked isprogressively increased by decreasing the amplitude of the currentapplied by efferent anode set 44. The action potentials induced bycathode 46 in the fibers now not blocked travel unimpeded towards theheart. As a result, the parasympathetic stimulation delivered to theheart is progressively increased in a smaller-to-larger diameter fiberorder, mimicking the body's natural method of increasing stimulation. Inaddition, for any given number of fibers stimulated (and not blocked),the amount of stimulation delivered to the heart can be increased byincreasing the amplitude and/or frequency of the current applied tovagus nerve 36.

[0206] In order to suppress artificially-induced afferent actionpotentials from traveling towards the brain in response to the cathodicstimulation, control unit 20 preferably drives electrode device 40 toinhibit fibers 50, 52, 54 and 56 using afferent anodal current fromafferent anode set 45. When the afferent-directed action potentialsinduced by cathode 46 in all of the fibers reach the hyperpolarizedregion in all of the fibers adjacent to afferent anode set 45, theaction potentials are blocked. Blocking these afferent action potentialsgenerally minimizes any unintended side effects, such as undesired orcounterproductive feedback to the brain, that might be caused by theseaction potentials. Anode 45 b is shown generating less current thananode 45 a in order to minimize the virtual cathode effect in thedirection of the brain, as described above.

[0207] In a preferred embodiment of the present invention, stimulationof the vagus nerve is applied responsive to one or more sensedparameters. Control unit 20 is preferably configured to commence or haltstimulation, or to vary the amount and/or timing of stimulation in orderto achieve a desired target heart rate, typically based on configurationvalues and on parameters including one or more of the following:

[0208] Heart rate—the control unit can be configured to drive electrodedevice 40 to stimulate the vagus nerve only when the heart rate exceedsa certain value.

[0209] ECG readings—the control unit can be configured to driveelectrode device 40 to stimulate the vagus nerve based on certain ECGreadings, such as readings indicative of designated forms of arrhythmia.Additionally, ECG readings are preferably used for achieving a desireheart rate, as described below with reference to FIG. 5.

[0210] Blood pressure—the control unit can be configured to regulate thecurrent applied by electrode device 40 to the vagus nerve when bloodpressure exceeds a certain threshold or falls below a certain threshold.

[0211] Indicators of decreased cardiac contractility—these indicatorsinclude left ventricular pressure (LVP). When LVP and/or d(LVP)/dtexceeds a certain threshold or falls below a certain threshold, controlunit 20 can drive electrode device 40 to regulate the current applied byelectrode device 40 to the vagus nerve.

[0212] Motion of the patient—the control unit can be configured tointerpret motion of the patient as an indicator of increased exertion bythe patient, and appropriately reduce parasympathetic stimulation of theheart in order to allow the heart to naturally increase its rate.

[0213] Heart rate variability—the control unit can be configured todrive electrode device 40 to stimulate the vagus nerve based on heartrate variability, which is preferably calculated based on certain ECGreadings.

[0214] Norepinephrine concentration—the control unit can be configuredto drive electrode device 40 to stimulate the vagus nerve based onnorepinephrine concentration.

[0215] Cardiac output—the control unit can be configured to driveelectrode device 40 to stimulate the vagus nerve based on cardiacoutput, which is preferably determined using impedance cardiography.

[0216] The parameters and behaviors included in this list are forillustrative purposes only, and other possible parameters and/orbehaviors will readily present themselves to those skilled in the art,having read the disclosure of the present patent application.

[0217] In embodiments of the present invention in which vagalstimulation system 18 comprises implanted device 25 for monitoring andcorrecting the heart rate, control unit 20 preferably uses measuredparameters received from device 25 as additional inputs for determiningthe level and/or type of stimulation to apply. Control unit 20preferably coordinates its behavior with the behavior of device 25.Control unit 20 and device 25 preferably share sensors 26 in order toavoid redundancy in the combined system.

[0218] Optionally, vagal stimulation system 18 comprises a patientoverride, such as a switch that can be activated by the patient using anexternal magnet. The override preferably can be used by the patient toactivate vagal stimulation, for example in the event of arrhythmiaapparently undetected by the system, or to deactivate vagal stimulation,for example in the event of apparently undetected physical exertion.

[0219]FIG. 5 is a simplified illustration of an ECG recording 70 andexample timelines 72 and 76 showing the timing of the application of aseries of stimulation pulses 74, in accordance with a preferredembodiment of the present invention. Stimulation is preferably appliedto vagus nerve 36 in a closed-loop system in order to achieve andmaintain the desired target heart rate, determined as described above.Precise graded slowing of the heart beat is preferably achieved byvarying the number of nerve fibers stimulated, in a smaller-to-largerdiameter order, and/or the intensity of vagus nerve stimulation.Stimulation with blocking, as described herein, is preferably appliedduring each cardiac cycle in a series of pulses 74, preferablycontaining between about 1 and about 20 pulses, each of about 1-3milliseconds duration, over a period of about 1-200 milliseconds.Advantageously, such short pulse durations generally do notsubstantially block or interfere with the natural efferent or afferentaction potentials traveling along the vagus nerve. Additionally, thenumber of pulses and/or their duration is sometimes varied in order tofacilitate achievement of precise graded slowing of the heart beat.

[0220] To apply the closed-loop system, preferably the target heart rateis expressed as a ventricular R-R interval (shown as the intervalbetween R₁ and R₂ in FIG. 5). The actual R-R interval is measured inreal time and compared with the target R-R interval. The differencebetween the two intervals is defined as a control error. Control unit 20calculates the change in stimulation necessary to move the actual R-Rtowards the target R-R, and drives electrode device 40 to apply the newcalculated stimulation. Intermittently, e.g., every 1, 10, or 100 beats,measured R-R intervals or average R-R intervals are evaluated, andstimulation of the vagus nerve is modified accordingly.

[0221] The delay before applying pulse series 74 in each cardiac cycleinfluences the R-R interval achieved at any given level of stimulation.This delay can be measured from a number of sensed physiologicalparameters (“initiation physiological parameters”), including sensedpoints in the cardiac cycle, including P-, Q-, R-, S- and T-waves.Preferably the delay is measured from the P-wave, which indicates atrialcontraction. Alternatively, the delay is measured from the R-wave,particularly when the P-wave is not easily detected. Timeline A 72 andTimeline B 76 show the delays, t_(R) and t_(P) measured from R and P,respectively.

[0222] When a closed-loop system is used with a constant t, a desiredtarget R-R interval can be achieved, but a substantial R-R intervalvariability on a beat-to-beat basis often occurs, as described in ZhangY et al., cited above. The techniques described herein, by varying t inreal time (that is, using t as a controlled parameter), rather thanusing a constant t, generally substantially reduce this R-R intervalvariability.

[0223] Preferably, t from either R or P is calculated in real time usinga function, the inputs of which include one or more numeric parametersand one or more ECG values or other physiological values (“terminationphysiological parameters”) measured in real time. The terminationphysiological parameters determine how long the delay t will continuebefore pulse series 74 is begun. The values of the numeric parametersand which physiological inputs to use are preferably determined during acalibration procedure, as described below, or may be based on theparticular heart condition and/or medical history of the patient beingtreated.

[0224] For example, t may be measured from R or P, as shown in timelineA 72 and timeline B 76, respectively, and the function may take the formof:

t=C+K*f(R-R interval, P-R interval ),

[0225] wherein C and K are constants optimized to minimize R-R intervalvariability, and the R-R interval and/or P-R interval are inputs to thefunction. Alternatively or additionally, the function includes as inputsother ECG values and/or sensed physiological parameters, such asatrioventricular (AV) delay, blood pressure, or respiration. For someapplications, the function includes other types of linear and non-linearrelationships, such as exponentials or differentials.

[0226] Typically, the function uses the R-R or P-R interval, or othersensed parameters, that were measured in the previous cardiac cycle, inorder to maximize responsiveness of the function to real-time changes inheart rate. Alternatively, the interval or other sensed parameters arecalculated as a running average of intervals or parameters measuredduring a certain number of previous heart cycles, in order to smooth thevariability of t from beat to beat.

[0227] In a preferred embodiment, t is obtained in real time from alookup table, the inputs to which include one or more ECG or otherphysiological values. The lookup table is typically either populatedduring a calibration procedure, or with fixed values for a particularheart condition.

[0228] To facilitate the above process, a calibration procedure ispreferably performed. This procedure is typically performed by aphysician for an individual patient prior to or soon after installationof vagal stimulation system 18, or, alternatively or additionally, by oron behalf of the manufacturer of the system prior to its sale. Duringcalibration for an individual patient, the physician preferablydetermines suitable parameters for real-time determination of t byrecording ECGs of the patient under different levels of heart stresswhile applying stimulation with a range of values of t.

[0229] In a preferred embodiment, vagal stimulation system 18 is furtherconfigured to apply stimulation responsive to pre-set time parameters,such as intermittently, constantly, or based on the time of day.

[0230] Optionally, the stimulation applied by vagal stimulation system18 is applied in conjunction with or separately from stimulation ofsympathetic nerves innervating the heart. Such sympathetic stimulationcan be applied using techniques of smaller-to-larger diameter fiberrecruitment, as described herein, or other nerve stimulation techniquesknown in the art.

[0231] Alternatively or additionally, the techniques ofsmaller-to-larger diameter fiber recruitment and t control are appliedin conjunction with methods and apparatus described in one or more ofthe patents, patent applications, articles and books cited herein.

[0232] Although preferred embodiments of the present invention aredescribed herein with respect to treating heart conditions, it is to beunderstood that the scope of the present invention includes utilizingthe techniques described herein to controllably stimulate the vagusnerve to facilitate other treatments, e.g., to treat depression,epilepsy, spasticity, obesity, syncope, brain disorders,gastrointestinal tract disorders, renal disorders, pancreatic disorders,or lung disorders. In particular, the techniques described herein may beperformed in combination with other techniques, which are well known inthe art or which are described in the references cited herein, thatstimulate the vagus nerve in order to achieve a desired therapeutic end.

[0233] For some applications, techniques described herein are used toapply controlled stimulation to one or more of the following: thelacrimal nerve, the salivary nerve, the vagus nerve, the pelvicsplanchnic nerve, or one or more sympathetic or parasympatheticautonomic nerves. Such controlled stimulation may be used, for example,to regulate or treat a condition of the lung, heart, stomach, pancreas,small intestine, liver, spleen, kidney, bladder, rectum, largeintestine, reproductive organs, or adrenal gland.

[0234] It will be appreciated by persons skilled in the art that thepresent invention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. Apparatus for treating a heart condition of a subject, comprising: anelectrode device, adapted to be coupled to a vagus nerve of the subject;and a control unit, adapted to: drive the electrode device to apply tothe vagus nerve a stimulating current, which is capable of inducingaction potentials in a therapeutic direction in a first set and a secondset of nerve fibers of the vagus nerve, and drive the electrode deviceto apply to the vagus nerve an inhibiting current, which is capable ofinhibiting the induced action potentials traveling in the therapeuticdirection in the second set of nerve fibers, the nerve fibers in thesecond set having generally larger diameters than the nerve fibers inthe first set.
 2. Apparatus according to claim 1, wherein thetherapeutic direction is an efferent therapeutic direction towards aheart of the subject, and wherein the control unit is adapted to: drivethe electrode device to apply to the vagus nerve the stimulatingcurrent, configured to induce action potentials in the efferenttherapeutic direction in the first and the second set of nerve fibers,and drive the electrode device to apply to the vagus nerve theinhibiting current, configured to inhibit the induced action potentialstraveling in the efferent therapeutic direction in the second set ofnerve fibers.
 3. Apparatus according to claim 1, wherein the therapeuticdirection is an afferent therapeutic direction towards a brain of thesubject, and wherein the control unit is adapted to: drive the electrodedevice to apply to the vagus nerve the stimulating current, configuredto induce action potentials in the afferent therapeutic direction in thefirst and the second set of nerve fibers, and drive the electrode deviceto apply to the vagus nerve the inhibiting current, configured toinhibit the induced action potentials traveling in the afferenttherapeutic direction in the second set of nerve fibers.
 4. Apparatusaccording to claim 1, wherein the control unit is adapted to increase anumber of action potentials traveling in the therapeutic direction bydecreasing an amplitude of the applied inhibiting current.
 5. Apparatusaccording to claim 1, wherein the control unit is adapted to decrease anumber of action potentials traveling in the therapeutic direction byincreasing an amplitude of the applied inhibiting current.
 6. Apparatusaccording to claim 1, wherein the heart condition includes heartfailure, and the apparatus is adapted to treat the heart condition. 7.Apparatus according to claim 1, wherein the heart condition includescardiac arrhythmia, and the apparatus is adapted to treat the heartcondition.
 8. Apparatus according to claim 1, comprising an override,adapted to be used by the subject so as to influence the application bythe electrode device of the stimulating and inhibiting currents. 9.Apparatus according to claim 1, comprising a pacemaker, wherein thecontrol unit is adapted to drive the pacemaker to apply pacing pulses toa heart of the subject.
 10. Apparatus according to claim 1, comprisingan implantable cardioverter defibrillator (ICD), wherein the controlunit is adapted to drive the ICD to apply energy to a heart of thesubject.
 11. Apparatus according to claim 1, wherein the control unit isadapted to drive the electrode device to apply the stimulating currentin a series of pulses.
 12. Apparatus according to claim 1, wherein thecontrol unit is adapted to drive the electrode device to apply theinhibiting current in a series of pulses.
 13. Apparatus according toclaim 1, wherein the control unit is adapted to receive an electricalsignal from the electrode device, and to drive the electrode device toregulate the stimulating current responsive to the electrical signal.14. Apparatus according to claim 1, wherein the control unit is adaptedto receive an electrical signal from the electrode device, and to drivethe electrode device to regulate the inhibiting current responsive tothe electrical signal.
 15. Apparatus according to claim 1, wherein theelectrode device comprises a cathode, adapted to apply the stimulatingcurrent, and a primary set of anodes, adapted to apply the inhibitingcurrent.
 16. Apparatus according to claim 15, wherein the primary set ofanodes comprises a primary anode and a secondary anode, adapted to bedisposed so that the primary anode is located between the secondaryanode and the cathode, and wherein the secondary anode is adapted toapply a current with an amplitude less than about one half an amplitudeof a current applied by the primary anode.
 17. Apparatus according toclaim 1, wherein the control unit is adapted to drive the electrodedevice to apply the stimulating current so as to regulate a heart rateof the subject.
 18. Apparatus according to claim 17, wherein the controlunit is adapted to drive the electrode device to regulate an amplitudeof the stimulating current so as to regulate the heart rate of thesubject.
 19. Apparatus according to claim 1, wherein the control unit isadapted to drive the electrode device to apply the inhibiting current soas to regulate a heart rate of the subject.
 20. Apparatus according toclaim 19, wherein the control unit is adapted to drive the electrodedevice to regulate an amplitude of the inhibiting current so as toregulate the heart rate of the subject.
 21. Apparatus according to claim1, wherein the control unit is adapted to drive the electrode device toapply the stimulating and inhibiting currents in a series of pulses. 22.Apparatus according to claim 21, wherein the control unit is adapted todrive the electrode device to apply the stimulating and inhibitingcurrents in a series of about one to 20 pulses.
 23. Apparatus accordingto claim 21, wherein the control unit is adapted to drive the electrodedevice to configure the pulses to have a duration of between about oneand three milliseconds.
 24. Apparatus according to claim 21, wherein thecontrol unit is adapted to drive the electrode device to apply thestimulating and inhibiting currents in the series of pulses over aperiod of between about one and about 200 milliseconds.
 25. Apparatusaccording to claim 21, wherein the control unit is adapted to drive theelectrode device to apply the stimulating and inhibiting currents in theseries of pulses so as to regulate a heart rate of the subject. 26.Apparatus according to claim 25, wherein the control unit is adapted toregulate the number of pulses in the series of pulses so as to regulatethe heart rate of the subject.
 27. Apparatus according to claim 25,wherein the control unit is adapted to regulate a duration of each pulseso as to regulate the heart rate of the subject.
 28. Apparatus accordingto claim 25, wherein the control unit is adapted to vary a length of aperiod of application of the series of pulses so as to regulate theheart rate of the subject.
 29. Apparatus according to claim 1, whereinthe control unit is adapted to drive the electrode device to apply tothe vagus nerve a second inhibiting current, which is capable ofinhibiting device-induced action potentials traveling in anon-therapeutic direction opposite the therapeutic direction in thefirst and second sets of nerve fibers.
 30. Apparatus according to claim29, wherein the control unit is adapted to drive the electrode device toapply the second inhibiting current to the vagus nerve at a primary anda secondary location, the primary location located between the secondarylocation and an application location of the stimulating current, and toapply at the secondary location a current with an amplitude less thanabout one half an amplitude of a current applied at the primarylocation.
 31. Apparatus according to claim 1, comprising a sensor unit,wherein the control unit is adapted to receive at least one sensedparameter from the sensor unit, and to drive the electrode device toapply the stimulating and inhibiting currents responsive to the at leastone sensed parameter.
 32. Apparatus according to claim 31, wherein thecontrol unit is adapted to determine a target heart rate of the subjectresponsive to the at least one sensed parameter, and wherein the controlunit is adapted to drive the electrode device to apply the stimulatingand inhibiting currents so as to adjust a heart rate of the subjecttowards the target heart rate.
 33. Apparatus according to claim 31,wherein the sensor unit comprises a blood pressure sensor, wherein theat least one sensed parameter includes a blood pressure of the subject,and wherein the control unit is adapted to receive the at least onesensed parameter from the blood pressure sensor.
 34. Apparatus accordingto claim 31, wherein the sensor unit comprises a left ventricularpressure (LVP) sensor, wherein the at least one sensed parameterincludes an LVP of the subject, and wherein the control unit is adaptedto receive the at least one sensed parameter from the LVP sensor. 35.Apparatus according to claim 31, wherein the sensor unit comprises aleft ventricular pressure (LVP) sensor, wherein the at least one sensedparameter includes a time derivative of an LVP of the subject, andwherein the control unit is adapted to receive the at least one sensedparameter from the LVP sensor.
 36. Apparatus according to claim 31,wherein the at least one sensed parameter includes an indicator ofdecreased cardiac contractility, and wherein the control unit is adaptedto receive the indicator of decreased cardiac contractility. 37.Apparatus according to claim 31, wherein the sensor unit comprises anaccelerometer, wherein the at least one sensed parameter includes motionof the subject, and wherein the control unit is adapted to receive theat least one sensed parameter from the accelerometer.
 38. Apparatusaccording to claim 31, wherein the sensor unit comprises a detector ofnorepinephrine concentration in the subject, wherein the at least onesensed parameter includes a norepinephrine concentration, and whereinthe control unit is adapted to receive the at least one sensed parameterfrom the detector.
 39. Apparatus according to claim 31, wherein thesensor unit comprises an impedance cardiography sensor, wherein the atleast one sensed parameter includes a parameter generated by theimpedance cardiography sensor, and wherein the control unit is adaptedto receive the at least one sensed parameter from the detector. 40.Apparatus according to claim 31, wherein the at least one sensedparameter includes an indicator of cardiac output, and wherein thecontrol unit is adapted to receive the indicator of cardiac output. 41.Apparatus according to claim 31, wherein the sensor unit comprises anelectrocardiogram (ECG) monitor, wherein the at least one sensedparameter includes an ECG value, and wherein the control unit is adaptedto receive the at least one sensed parameter from the ECG monitor. 42.Apparatus according to claim 41, wherein the at least one sensedparameter includes an ECG reading indicative of a presence ofarrhythmia, and wherein the control unit is adapted to receive the atleast one sensed parameter from the ECG monitor.
 43. Apparatus accordingto claim 31, wherein the at least one sensed parameter includes anindication of a heart rate of the subject, and wherein the control unitis adapted to receive the indication of the heart rate.
 44. Apparatusaccording to claim 43, wherein the at least one sensed parameterincludes indications of a plurality of heart rates of the subject at arespective plurality of points in time, and wherein the control unit isadapted to receive the at least one sensed parameter and to determine ameasure of variability of heart rate responsive thereto.
 45. Apparatusaccording to claim 31, wherein the sensor unit is adapted to sense aninitiation physiological parameter and a termination physiologicalparameter of the subject, and wherein the control unit is adapted todrive the electrode device to apply the stimulating and inhibitingcurrents to the vagus nerve after a delay, to initiate the delayresponsive to the sensing of the initiation physiological parameter, andto set a length of the delay responsive to the termination physiologicalparameter.
 46. Apparatus according to claim 45, wherein the control unitis adapted to determine a target heart rate of the subject responsive tothe at least one sensed parameter, and wherein the control unit isadapted to set the delay so as to adjust the heart rate towards thetarget heart rate.
 47. Apparatus according to claim 45, wherein thetermination physiological parameter includes an atrioventricular (AV)delay of the subject, and wherein the control unit is adapted to set thelength of the delay responsive to the AV delay.
 48. Apparatus accordingto claim 45, wherein the sensor unit comprises an electrocardiogram(ECG) monitor.
 49. Apparatus according to claim 48, wherein theinitiation physiological parameter includes a P-wave of a cardiac cycleof the subject, and wherein the control unit is adapted to initiate thedelay responsive to the sensing of the P-wave.
 50. Apparatus accordingto claim 48, wherein the initiation physiological parameter includes anR-wave of a cardiac cycle of the subject, and wherein the control unitis adapted to initiate the delay responsive to the sensing of theR-wave.
 51. Apparatus according to claim 48, wherein the terminationphysiological parameter includes a difference in time between twofeatures of an ECG signal recorded by the ECG monitor, and wherein thecontrol unit is adapted to set the length of the delay responsive to thedifference in time between the two features.
 52. Apparatus according toclaim 51, wherein the termination physiological parameter includes anR-R interval between a sensing of an R-wave of a first cardiac cycle ofthe subject and a sensing of an R-wave of a next cardiac cycle of thesubject, and wherein the control unit is adapted to set the length ofthe delay responsive to the R-R interval.
 53. Apparatus according toclaim 51, wherein the termination physiological parameter includes a P-Rinterval between a sensing of a P-wave of a cardiac cycle of the subjectand a sensing of an R-wave of the cardiac cycle, and wherein the controlunit is adapted to set the length of the delay responsive to the P-Rinterval.
 54. Apparatus for treating a heart condition of a subject,comprising: a cathode, adapted to apply to a vagus nerve of the subjecta stimulating current which is capable of inducing action potentials inthe vagus nerve; and a primary and a secondary anode, adapted to bedisposed so that the primary anode is located between the secondaryanode and the cathode, and adapted to apply to the vagus nerverespective primary and secondary inhibiting currents which are capableof inhibiting action potentials in the vagus nerve.
 55. Apparatusaccording to claim 54, wherein the primary and secondary anodes areadapted to be placed between about 0.5 and about 2.0 millimeters apartfrom one another.
 56. Apparatus according to claim 54, wherein thesecondary anode is adapted to apply the secondary inhibiting currentwith an amplitude equal to between about 2 and about 5 milliamps. 57.Apparatus according to claim 54, wherein the secondary anode is adaptedto apply the secondary inhibiting current with an amplitude less thanabout one half an amplitude of the primary inhibiting current applied bythe primary anode.
 58. Apparatus according to claim 54, wherein theprimary anode comprises a ring electrode adapted to apply a generallyuniform current around a circumference of the vagus nerve.
 59. Apparatusaccording to claim 54, wherein the secondary anode comprises a ringelectrode adapted to apply a generally uniform current around acircumference of the vagus nerve.
 60. Apparatus according to claim 54,wherein the cathode comprises a ring electrode adapted to apply agenerally uniform current around a circumference of the vagus nerve. 61.Apparatus according to claim 54, comprising a tertiary anode, adapted tobe disposed such that the secondary anode is between the tertiary anodeand the primary anode.
 62. Apparatus according to claim 54, wherein theheart condition includes heart failure, and the apparatus is adapted totreat the heart condition.
 63. Apparatus according to claim 54, whereinthe heart condition includes cardiac arrhythmia, and the apparatus isadapted to treat the heart condition.
 64. Apparatus according to claim54, comprising an override, adapted to be used by the subject so as toinfluence the application by the cathode of the stimulating current andby the anodes of the inhibiting current.
 65. Apparatus according toclaim 54, comprising a pacemaker, adapted to apply pacing pulses to aheart of the subject.
 66. Apparatus according to claim 54, comprising animplantable cardioverter defibrillator (ICD), adapted to apply energy toa heart of the subject.
 67. Apparatus according to claim 54, wherein theelectrode device comprises an efferent edge, wherein the cathode isadapted to be disposed closer than the anodes to the efferent edge ofthe electrode device.
 68. Apparatus according to claim 54, wherein thecathode is adapted to apply the stimulating current so as to regulate aheart rate of the subject.
 69. Apparatus according to claim 54, whereinthe anodes are adapted to apply the inhibiting current so as to regulatea heart rate of the subject.
 70. Apparatus according to claim 54,wherein the cathode comprises a plurality of discrete cathodes, adaptedto be disposed at respective positions around an axis of the vagusnerve, so as to selectively stimulate nerve fibers of the vagus nerveresponsive to the positions of the nerve fibers in the vagus nerve. 71.Apparatus according to claim 54, wherein the primary anode comprises aplurality of discrete primary anodes, adapted to be disposed atrespective positions around an axis of the vagus nerve.
 72. Apparatusaccording to claim 71, wherein the secondary anode comprises a pluralityof discrete secondary anodes, adapted to be disposed at respectivepositions around the axis of the vagus nerve.
 73. Apparatus according toclaim 54, comprising a set of one or more blocking anodes, adapted to bedisposed such that the cathode is between the set of blocking anodes andthe primary anode, and adapted to apply to the vagus nerve a currentwhich is capable of inhibiting action potentials propagating in thevagus nerve in a direction from the cathode towards the set of blockinganodes.
 74. Apparatus according to claim 73, wherein the set of blockinganodes comprises a first anode and a second anode, adapted to bedisposed such that the first anode is located between the second anodeand the cathode, and wherein the second anode is adapted to apply acurrent with an amplitude less than about one half an amplitude of acurrent applied by the first anode.
 75. Apparatus according to claim 54,wherein the electrode device comprises an afferent edge, wherein thecathode is adapted to be disposed closer than the anodes to the afferentedge of the electrode device.
 76. Apparatus according to claim 75,wherein the apparatus is adapted to increase a number of actionpotentials traveling in an efferent direction by decreasing an amplitudeof the primary inhibiting current.
 77. Apparatus according to claim 54,comprising a cuff, and an electrically-insulating element coupled to aninner portion of the cuff, wherein the primary anode and the cathode areadapted to be mounted in the cuff and separated from one another by theinsulating element.
 78. Apparatus according to claim 77, wherein theprimary and secondary anodes and the cathode are adapted to be recessedin the cuff so as not to be in direct contact with the vagus nerve. 79.Apparatus according to claim 54, comprising a control unit, adapted todrive the cathode and the anodes to apply the respective currents to thevagus nerve, so as to treat the subject.
 80. Apparatus according toclaim 79, wherein the control unit is adapted to receive an electricalsignal from an electrode, including at least one of: the cathode, theprimary anode, and the secondary anode, and to drive the cathode toregulate the stimulating current responsive to the electrical signal.81. Apparatus according to claim 79, wherein the control unit is adaptedto receive an electrical signal from an electrode, including at leastone of: the cathode, the primary anode, and the secondary anode, and todrive the anodes to regulate the inhibiting currents responsive to theelectrical signal.
 82. Apparatus according to claim 79, comprising asensor unit, wherein the control unit is adapted to receive at least onesensed parameter from the sensor unit, and to drive the cathode and theanodes to apply the respective currents to the vagus nerve responsive tothe at least one sensed parameter.
 83. Apparatus according to claim 82,wherein the control unit is adapted to determine a target heart rate ofthe subject responsive to the at least one sensed parameter, and whereinthe control unit is adapted to drive the cathode and the anodes to applythe respective currents so as to adjust a heart rate of the subjecttowards the target heart rate.
 84. Apparatus according to claim 82,wherein the sensor unit comprises a blood pressure sensor, wherein theat least one sensed parameter includes a blood pressure of the subject,and wherein the control unit is adapted to receive the at least onesensed parameter from the blood pressure sensor.
 85. Apparatus accordingto claim 82, wherein the sensor unit comprises a left ventricularpressure (LVP) sensor, wherein the at least one sensed parameterincludes an LVP of the subject, and wherein the control unit is adaptedto receive the at least one sensed parameter from the LVP sensor. 86.Apparatus according to claim 82, wherein the sensor unit comprises aleft ventricular pressure (LVP) sensor, wherein the at least one sensedparameter includes a time derivative of an LVP of the subject, andwherein the control unit is adapted to receive the at least one sensedparameter from the LVP sensor.
 87. Apparatus according to claim 82,wherein the at least one sensed parameter includes an indicator ofdecreased cardiac contractility, and wherein the control unit is adaptedto receive the indicator of decreased cardiac contractility. 88.Apparatus according to claim 82, wherein the sensor unit comprises anaccelerometer, wherein the at least one sensed parameter includes motionof the subject, and wherein the control unit is adapted to receive theat least one sensed parameter from the accelerometer.
 89. Apparatusaccording to claim 82, wherein the sensor unit comprises a detector ofnorepinephrine concentration in the subject, wherein the at least onesensed parameter includes a norepinephrine concentration, and whereinthe control unit is adapted to receive the at least one sensed parameterfrom the detector.
 90. Apparatus according to claim 82, wherein thesensor unit comprises an impedance cardiography sensor, wherein the atleast one sensed parameter includes a parameter generated by theimpedance cardiography sensor, and wherein the control unit is adaptedto receive the at least one sensed parameter from the sensor unit. 91.Apparatus according to claim 82, wherein the at least one sensedparameter includes an indicator of cardiac output, and wherein thecontrol unit is adapted to receive the indicator of cardiac output. 92.Apparatus according to claim 82, wherein the at least one sensedparameter includes an indication of a heart rate of the subject, andwherein the control unit is adapted to receive the indication of theheart rate.
 93. Apparatus according to claim 92, wherein the at leastone sensed parameter includes indications of a plurality of heart ratesof the subject at a respective plurality of points in time, and whereinthe control unit is adapted to receive the at least one sensed parameterand to determine a measure of variability of heart rate responsivethereto.
 94. Apparatus according to claim 82, wherein the sensor unitcomprises an electrocardiogram (ECG) monitor, and wherein the controlunit is adapted to receive at least one sensed parameter from the ECGmonitor.
 95. Apparatus according to claim 94, wherein the at least onesensed parameter includes an ECG reading indicative of a presence ofarrhythmia, and wherein the control unit is adapted to receive the atleast one sensed parameter from the ECG monitor.
 96. Apparatus accordingto claim 54, wherein the cathode is adapted to apply the stimulatingcurrent and the anodes are adapted to apply the inhibiting current so asto regulate a heart rate of the subject.
 97. Apparatus according toclaim 96, wherein the cathode is adapted to vary an amplitude of theapplied stimulating current and the anodes are adapted to vary anamplitude of the applied inhibiting current so as to regulate a heartrate of the subject.
 98. Apparatus according to claim 96, comprising asensor unit, adapted to sense an initiation physiological parameter anda termination physiological parameter of the subject, wherein thecontrol unit is adapted to receive the initiation and terminationphysiological parameters from the sensor unit, to drive the electrodedevice to apply the stimulating and inhibiting currents to the vagusnerve after a delay, to initiate the delay responsive to the sensing ofthe initiation physiological parameter, and to set a length of the delayresponsive to the termination physiological parameter.
 99. Apparatusaccording to claim 98, wherein the sensor unit is adapted to sense atleast one additional sensed parameter, and wherein the control unit isadapted to receive the at least one additional sensed parameter from thesensor unit, to determine a target heart rate of the subject responsiveto the at least one additional sensed parameter, and to set the delay soas to adjust the heart rate towards the target heart rate. 100.Apparatus according to claim 98, wherein the termination physiologicalparameter includes an atrioventricular (AV) delay of the subject, andwherein the control unit is adapted to set the length of the delayresponsive to the AV delay.
 101. Apparatus according to claim 98,wherein the sensor unit comprises an electrocardiogram (ECG) monitor.102. Apparatus according to claim 101, wherein the initiationphysiological parameter includes a P-wave of a cardiac cycle of thesubject, and wherein the control unit is adapted to initiate the delayresponsive to the sensing of the P-wave.
 103. Apparatus according toclaim 101, wherein the initiation physiological parameter includes anR-wave of a cardiac cycle of the subject, and wherein the control unitis adapted to initiate the delay responsive to the sensing of theR-wave.
 104. Apparatus according to claim 101, wherein the terminationphysiological parameter includes a difference between two features of anECG signal recorded by the ECG monitor, and wherein the control unit isadapted to set the length of the delay responsive to the difference intime between the two features.
 105. Apparatus according to claim 104,wherein the termination physiological parameter includes an R-R intervalbetween a sensing of an R-wave of a first cardiac cycle of the subjectand a sensing of an R-wave of a next cardiac cycle of the subject, andwherein the control unit is adapted to set the length of the delayresponsive to the R-R interval.
 106. Apparatus according to claim 104,wherein the termination physiological parameter includes a P-R intervalbetween a sensing of a P-wave of a cardiac cycle of the subject and asensing of an R-wave of the cardiac cycle, and wherein the control unitis adapted to set the length of the delay responsive to the P-Rinterval.
 107. Apparatus according to claim 54, wherein the cathode andanodes are adapted to apply the stimulating current and the inhibitingcurrent, respectively, in a series of pulses.
 108. Apparatus accordingto claim 107, wherein the cathode and anodes are adapted to apply thestimulating current and the inhibiting current, respectively, in aseries of between about one and 20 pulses.
 109. Apparatus according toclaim 107, wherein the cathode and anodes are adapted to apply thestimulating current and the inhibiting current, respectively, in aseries of pulses, each pulse with a duration of between about one andthree milliseconds.
 110. Apparatus according to claim 107, wherein thecathode and anodes are adapted to apply the stimulating current and theinhibiting current, respectively, in the series of pulses over a periodof between about one and about 200 milliseconds.
 111. Apparatusaccording to claim 107, wherein the cathode and anodes are adapted toapply the stimulating current and the inhibiting current, respectively,in the series of pulses so as to regulate a heart rate of the subject.112. Apparatus according to claim 111, wherein the cathode and theanodes are adapted to regulate the number of pulses in the series ofpulses so as to regulate the heart rate of the subject.
 113. Apparatusaccording to claim 111, wherein the cathode and the anodes are adaptedto regulate a duration of each pulse so as to regulate the heart rate ofthe subject.
 114. Apparatus according to claim 111, wherein the cathodeand the anodes are adapted to vary a length of a period of applicationof the series of pulses so as to regulate the heart rate of the subject.115. Apparatus for treating a heart condition of a subject, comprising:an electrode device, adapted to be coupled to a vagus nerve of thesubject; a sensor unit, adapted to sense an initiation physiologicalparameter and a termination physiological parameter of the subject; anda control unit, adapted to: drive the electrode device to apply to thevagus nerve, after a delay, a current which is capable of inducingaction potentials that propagate in the vagus nerve, initiate the delayresponsive to the sensing of the initiation physiological parameter, andset a length of the delay responsive to the termination physiologicalparameter.
 116. Apparatus according to claim 115, wherein the electrodedevice is adapted to apply a current that is capable of inducing actionpotentials that propagate in an efferent direction in the vagus nerve.117. Apparatus according to claim 115, wherein the electrode device isadapted to apply a current that is capable of inducing action potentialsthat propagate in an afferent direction in the vagus nerve. 118.Apparatus according to claim 115, wherein the heart condition includesheart failure, and the apparatus is adapted to treat the heartcondition.
 119. Apparatus according to claim 115, wherein the heartcondition includes cardiac arrhythmia, and the apparatus is adapted totreat the heart condition.
 120. Apparatus according to claim 115,wherein the sensor unit comprises a single sensor, adapted to sense theinitiation physiological parameter and the termination physiologicalparameter.
 121. Apparatus according to claim 115, wherein thetermination physiological parameter includes an atrioventricular (AV)delay of the subject, and wherein the control unit is adapted to set thelength of the delay responsive to the AV delay.
 122. Apparatus accordingto claim 115, wherein the termination physiological parameter includes arespiration parameter of the subject, and wherein the control unit isadapted to set the length of the delay responsive to the respirationparameter.
 123. Apparatus according to claim 115, wherein the controlunit is adapted to: drive the electrode device to apply to the vagusnerve a stimulating current, which is capable of inducing actionpotentials in a therapeutic direction in a first set and a second set ofnerve fibers of the vagus nerve, and drive the electrode device to applyto the vagus nerve an inhibiting current, which is capable of inhibitingthe induced action potentials traveling in the therapeutic direction inthe second set of nerve fibers, the nerve fibers in the second sethaving generally larger diameters than the nerve fibers in the firstset.
 124. Apparatus according to claim 115, wherein the electrode devicecomprises: a cathode, adapted to apply to the vagus nerve a stimulatingcurrent which is capable of inducing action potentials in the vagusnerve; and a primary and a secondary anode, adapted to be disposed sothat the primary anode is located between the secondary anode and thecathode, and adapted to apply to the vagus nerve an inhibiting currentwhich is capable of inhibiting action potentials in the vagus nerve.125. Apparatus according to claim 115, wherein the control unit isadapted to receive an electrical signal from the electrode device, andto drive the electrode device to regulate the current responsive to theelectrical signal.
 126. Apparatus according to claim 115, wherein thecontrol unit is adapted to drive the electrode device to apply thecurrent so as to regulate a heart rate of the subject.
 127. Apparatusaccording to claim 126, wherein the control unit is adapted to drive theelectrode device to vary an amplitude of the current so as to regulatethe heart rate of the subject.
 128. Apparatus according to claim 115,wherein the sensor unit comprises a blood pressure sensor. 129.Apparatus according to claim 128, wherein the termination physiologicalparameter includes a blood pressure of the subject, and wherein thecontrol unit is adapted to set the length of the delay responsive to theblood pressure.
 130. Apparatus according to claim 128, wherein thesensor unit is adapted to sense a rate-setting parameter of the subject,wherein the rate-setting parameter includes a blood pressure of thesubject, and wherein the control unit is adapted to receive therate-setting parameter from the sensor unit and to drive the electrodedevice to apply the current responsive to the rate-setting parameter.131. Apparatus according to claim 115, wherein the control unit isadapted to drive the electrode device to apply the current in a seriesof pulses.
 132. Apparatus according to claim 131, wherein the controlunit is adapted to drive the electrode device to apply the current in aseries of about one to 20 pulses.
 133. Apparatus according to claim 131,wherein the control unit is adapted to configure the pulses to have aduration of between about one and three milliseconds.
 134. Apparatusaccording to claim 131, wherein the control unit is adapted to drive theelectrode device to apply the current in the series of pulses over aperiod of between about one and about 200 milliseconds.
 135. Apparatusaccording to claim 131, wherein the control unit is adapted to drive theelectrode device to apply the current in the series of pulses so as toregulate a heart rate of the subject.
 136. Apparatus according to claim135, wherein the control unit is adapted to regulate a number of pulsesin the series of pulses so as to regulate the heart rate of the subject.137. Apparatus according to claim 135, wherein the control unit isadapted to regulate a duration of each pulse so as to regulate the heartrate of the subject.
 138. Apparatus according to claim 135, wherein thecontrol unit is adapted to vary a length of a period of application ofthe series of pulses so as to regulate the heart rate of the subject.139. Apparatus according to claim 115, wherein the sensor unit isadapted to sense a rate-setting parameter of the subject, and whereinthe control unit is adapted to receive the rate-setting parameter fromthe sensor unit and to drive the electrode device to apply the currentresponsive to the rate-setting parameter, so as to regulate a heart rateof the subject.
 140. Apparatus according to claim 139, wherein therate-setting parameter includes the initiation physiological parameter,and wherein the control unit is adapted to drive the electrode device toapply the current responsive to the initiation physiological parameterso as to regulate the heart rate of the subject.
 141. Apparatusaccording to claim 139, wherein the rate-setting parameter includes thetermination physiological parameter, and wherein the control unit isadapted to drive the electrode device to apply the current responsive tothe termination physiological parameter so as to regulate the heart rateof the subject.
 142. Apparatus according to claim 139, wherein thesensor unit comprises a left ventricular pressure (LVP) sensor, whereinthe rate-setting parameter includes an LVP of the subject, and whereinthe control unit is adapted to receive the LVP from the sensor unit, andto drive the electrode device to apply the current responsive to the LVPso as to regulate the heart rate of the subject.
 143. Apparatusaccording to claim 139, wherein the sensor unit comprises a leftventricular pressure (LVP) sensor, wherein the rate-setting parameterincludes a time derivative of an LVP of the subject, and wherein thecontrol unit is adapted to receive the LVP from the sensor unit, and todrive the electrode device to apply the current responsive to the timederivative of the LVP so as to regulate the heart rate of the subject.144. Apparatus according to claim 139, wherein the sensor unit comprisesan accelerometer, wherein the rate-setting parameter includes anindication of motion of the subject, and wherein the control unit isadapted to receive the indication of motion from the sensor unit, and todrive the electrode device to apply the current responsive to theindication of motion so as to regulate the heart rate of the subject.145. Apparatus according to claim 139, wherein the sensor unit comprisesa detector of norepinephrine concentration in the subject, wherein therate-setting parameter includes an indication of a norepinephrineconcentration, and wherein the control unit is adapted to receive theindication of the norepinephrine concentration from the sensor unit, andto drive the electrode device to apply the current responsive to theindication of the norepinephrine concentration so as to regulate theheart rate of the subject.
 146. Apparatus according to claim 139,wherein the sensor unit comprises an impedance cardiography sensor, andwherein the rate-setting parameter includes a parameter generated by theimpedance cardiography sensor, and wherein the control unit is adaptedto receive the parameter generated by the impedance cardiography sensorfrom the sensor unit, and to drive the electrode device to apply thecurrent responsive to the parameter generated by the impedancecardiography sensor so as to regulate the heart rate of the subject.147. Apparatus according to claim 139, wherein the rate-settingparameter includes an indicator of decreased cardiac contractility, andwherein the control unit is adapted to receive the indicator ofdecreased cardiac contractility from the sensor unit, and to drive theelectrode device to apply the current responsive to the indicator ofdecreased cardiac contractility so as to regulate the heart rate of thesubject.
 148. Apparatus according to claim 139, wherein the rate-settingparameter includes an indicator of cardiac output, and wherein thecontrol unit is adapted to receive the indicator of cardiac output fromthe sensor unit, and to drive the electrode device to apply the currentresponsive to the indicator of cardiac output so as to regulate theheart rate of the subject.
 149. Apparatus according to claim 139,wherein the rate-setting parameter includes an indication of a heartrate of the subject, and wherein the control unit is adapted to receivethe indication of the heart rate from the sensor unit, and to drive theelectrode device to apply the current responsive to the indication ofthe heart rate so as to regulate the heart rate of the subject. 150.Apparatus according to claim 149, wherein the rate-setting parameterincludes indications of a plurality of heart rates of the subject at arespective plurality of points in time, and wherein the control unit isadapted to receive the indications of the plurality of heart rates, andto drive the electrode device to apply the current responsive to theindications of the plurality of heart rates so as to regulate the heartrate of the subject.
 151. Apparatus according to claim 139, wherein thecontrol unit is adapted to determine a target heart rate of the subjectresponsive to the rate-setting parameter, and wherein the control unitis adapted to drive the electrode device to apply the current so as toadjust a heart rate of the subject towards the target heart rate. 152.Apparatus according to claim 151, wherein the control unit is adapted toset the length of the delay so as to adjust the heart rate towards thetarget heart rate.
 153. Apparatus according to claim 151, wherein thecontrol unit is adapted to access a lookup table of delays, and to setthe length of the delay using the lookup table and responsive to theinitiation and termination physiological parameters.
 154. Apparatusaccording to claim 115, wherein the sensor unit comprises anelectrocardiogram (ECG) monitor.
 155. Apparatus according to claim 154,wherein the initiation physiological parameter includes a P-wave of acardiac cycle of the subject, and wherein the control unit is adapted toinitiate the delay responsive to the sensing of the P-wave. 156.Apparatus according to claim 154, wherein the initiation physiologicalparameter includes an R-wave of a cardiac cycle of the subject, andwherein the control unit is adapted to initiate the delay responsive tothe sensing of the R-wave.
 157. Apparatus according to claim 154,wherein the initiation physiological parameter includes a Q-wave of acardiac cycle of the subject, and wherein the control unit is adapted toinitiate the delay responsive to the sensing of the Q-wave. 158.Apparatus according to claim 154, wherein the initiation physiologicalparameter includes a S-wave of a cardiac cycle of the subject, andwherein the control unit is adapted to initiate the delay responsive tothe sensing of the S-wave.
 159. Apparatus according to claim 154,wherein the termination physiological parameter includes a difference intime between two features of an ECG signal recorded by the ECG monitor,and wherein the control unit is adapted to set the length of the delayresponsive to the difference in time between the two features. 160.Apparatus according to claim 159, wherein the termination physiologicalparameter includes an R-R interval between a sensing of an R-wave of afirst cardiac cycle of the subject and a sensing of an R-wave of a nextcardiac cycle of the subject, and wherein the control unit is adapted toset the length of the delay responsive to the R-R interval. 161.Apparatus according to claim 160, wherein the termination physiologicalparameter includes an average of R-R intervals sensed for a number ofcardiac cycles, and wherein the control unit is adapted to set thelength of the delay responsive to the average of the R-R intervals. 162.Apparatus according to claim 159, wherein the termination physiologicalparameter includes a P-R interval between a sensing of a P-wave of acardiac cycle of the subject and a sensing of an R-wave of the cardiaccycle, and wherein the control unit is adapted to set the length of thedelay responsive to the P-R interval.
 163. Apparatus according to claim162, wherein the termination physiological parameter includes an averageof P-R intervals sensed for a number of cardiac cycles, and wherein thecontrol unit is adapted to set the length of the delay responsive to theaverage of the P-R intervals.
 164. Apparatus for treating a condition ofa subject, comprising: an electrode device, adapted to be coupled to anautonomic nerve of the subject; and a control unit, adapted to: drivethe electrode device to apply to the nerve a stimulating current, whichis capable of inducing action potentials in a therapeutic direction in afirst set and a second set of nerve fibers of the nerve, and drive theelectrode device to apply to the nerve an inhibiting current, which iscapable of inhibiting the induced action potentials traveling in thetherapeutic direction in the second set of nerve fibers, the nervefibers in the second set having generally larger diameters than thenerve fibers in the first set.
 165. Apparatus according to claim 164,wherein the autonomic nerve includes a lacrimal nerve, and wherein thecontrol unit is adapted to drive the electrode device to apply thestimulating and inhibiting currents to the lacrimal nerve. 166.Apparatus according to claim 164, wherein the autonomic nerve includes asalivary nerve, and wherein the control unit is adapted to drive theelectrode device to apply the stimulating and inhibiting currents to thesalivary nerve.
 167. Apparatus according to claim 164, wherein theautonomic nerve includes a vagus nerve, and wherein the control unit isadapted to drive the electrode device to apply the stimulating andinhibiting currents to the vagus nerve.
 168. Apparatus according toclaim 164, wherein the autonomic nerve includes a pelvic splanchnicnerve, and wherein the control unit is adapted to drive the electrodedevice to apply the stimulating and inhibiting currents to the pelvicsplanchnic nerve.
 169. Apparatus according to claim 164, wherein theautonomic nerve includes a sympathetic nerve, and wherein the controlunit is adapted to drive the electrode device to apply the stimulatingand inhibiting currents to the sympathetic nerve.
 170. Apparatusaccording to claim 164, wherein the control unit is adapted to drive theelectrode device to apply the stimulating and inhibiting currents to thenerve so as to affect behavior of a lung of the subject, so as to treatthe condition.
 171. Apparatus according to claim 164, wherein thecontrol unit is adapted to drive the electrode device to apply thestimulating and inhibiting currents to the nerve so as to affectbehavior of a stomach of the subject, so as to treat the condition. 172.Apparatus according to claim 164, wherein the control unit is adapted todrive the electrode device to apply the stimulating and inhibitingcurrents to the nerve so as to affect behavior of a pancreas of thesubject, so as to treat the condition.
 173. Apparatus according to claim164, wherein the control unit is adapted to drive the electrode deviceto apply the stimulating and inhibiting currents to the nerve so as toaffect behavior of a small intestine of the subject, so as to treat thecondition.
 174. Apparatus according to claim 164, wherein the controlunit is adapted to drive the electrode device to apply the stimulatingand inhibiting currents to the nerve so as to affect behavior of a liverof the subject, so as to treat the condition.
 175. Apparatus accordingto claim 164, wherein the control unit is adapted to drive the electrodedevice to apply the stimulating and inhibiting currents to the nerve soas to affect behavior of a spleen of the subject, so as to treat thecondition.
 176. Apparatus according to claim 164, wherein the controlunit is adapted to drive the electrode device to apply the stimulatingand inhibiting currents to the nerve so as to affect behavior of akidney of the subject, so as to treat the condition.
 177. Apparatusaccording to claim 164, wherein the control unit is adapted to drive theelectrode device to apply the stimulating and inhibiting currents to thenerve so as to affect behavior of a bladder of the subject, so as totreat the condition.
 178. Apparatus according to claim 164, wherein thecontrol unit is adapted to drive the electrode device to apply thestimulating and inhibiting currents to the nerve so as to affectbehavior of a rectum of the subject, so as to treat the condition. 179.Apparatus according to claim 164, wherein the control unit is adapted todrive the electrode device to apply the stimulating and inhibitingcurrents to the nerve so as to affect behavior of a large intestine ofthe subject, so as to treat the condition.
 180. Apparatus according toclaim 164, wherein the control unit is adapted to drive the electrodedevice to apply the stimulating and inhibiting currents to the nerve soas to affect behavior of a reproductive organ of the subject, so as totreat the condition.
 181. Apparatus according to claim 164, wherein thecontrol unit is adapted to drive the electrode device to apply thestimulating and inhibiting currents to the nerve so as to affectbehavior of an adrenal gland of the subject, so as to treat thecondition.
 182. Apparatus for treating a condition of a subject,comprising: a cathode, adapted to apply to an autonomic nerve of thesubject a stimulating current which is capable of inducing actionpotentials in the nerve; and a primary and a secondary anode, adapted tobe disposed so that the primary anode is located between the secondaryanode and the cathode, and adapted to apply to the nerve respectiveprimary and secondary inhibiting currents which are capable ofinhibiting action potentials in the nerve.
 183. Apparatus according toclaim 182, wherein the autonomic nerve includes a lacrimal nerve, andwherein the cathode and anodes are adapted to apply the stimulating andinhibiting currents, respectively, to the lacrimal nerve.
 184. Apparatusaccording to claim 182, wherein the autonomic nerve includes a salivarynerve, and wherein the cathode and anodes are adapted to apply thestimulating and inhibiting currents, respectively, to the salivarynerve.
 185. Apparatus according to claim 182, wherein the autonomicnerve includes a vagus nerve, and wherein the cathode and anodes areadapted to apply the stimulating and inhibiting currents, respectively,to the vagus nerve.
 186. Apparatus according to claim 182, wherein theautonomic nerve includes a pelvic splanchnic nerve, and wherein thecathode and anodes are adapted to apply the stimulating and inhibitingcurrents, respectively, to the pelvic splanchnic nerve.
 187. Apparatusaccording to claim 182, wherein the autonomic nerve includes asympathetic nerve, and wherein the cathode and anodes are adapted toapply the stimulating and inhibiting currents, respectively, to thesympathetic nerve.
 188. Apparatus according to claim 182, wherein thecathode and anodes are adapted to apply the stimulating and inhibitingcurrents, respectively, to the nerve so as to affect behavior of a lungof the subject, so as to treat the condition.
 189. Apparatus accordingto claim 182, wherein the cathode and anodes are adapted to apply thestimulating and inhibiting currents, respectively, to the nerve so as toaffect behavior of a stomach of the subject, so as to treat thecondition.
 190. Apparatus according to claim 182, wherein the cathodeand anodes are adapted to apply the stimulating and inhibiting currents,respectively, to the nerve so as to affect behavior of a pancreas of thesubject, so as to treat the condition.
 191. Apparatus according to claim182, wherein the cathode and anodes are adapted to apply the stimulatingand inhibiting currents, respectively, to the nerve so as to affectbehavior of a small intestine of the subject, so as to treat thecondition.
 192. Apparatus according to claim 182, wherein the cathodeand anodes are adapted to apply the stimulating and inhibiting currents,respectively, to the nerve so as to affect behavior of a liver of thesubject, so as to treat the condition.
 193. Apparatus according to claim182, wherein the cathode and anodes are adapted to apply the stimulatingand inhibiting currents, respectively, to the nerve so as to affectbehavior of a spleen of the subject, so as to treat the condition. 194.Apparatus according to claim 182, wherein the cathode and anodes areadapted to apply the stimulating and inhibiting currents, respectively,to the nerve so as to affect behavior of a kidney of the subject, so asto treat the condition.
 195. Apparatus according to claim 182, whereinthe cathode and anodes are adapted to apply the stimulating andinhibiting currents, respectively, to the nerve so as to affect behaviorof a bladder of the subject, so as to treat the condition. 196.Apparatus according to claim 182, wherein the cathode and anodes areadapted to apply the stimulating and inhibiting currents, respectively,to the nerve so as to affect behavior of a rectum of the subject, so asto treat the condition.
 197. Apparatus according to claim 182, whereinthe cathode and anodes are adapted to apply the stimulating andinhibiting currents, respectively, to the nerve so as to affect behaviorof a large intestine of the subject, so as to treat the condition. 198.Apparatus according to claim 182, wherein the cathode and anodes areadapted to apply the stimulating and inhibiting currents, respectively,to the nerve so as to affect behavior of a reproductive organ of thesubject, so as to treat the condition.
 199. Apparatus according to claim182, wherein the cathode and anodes are adapted to apply the stimulatingand inhibiting currents, respectively, to the nerve so as to affectbehavior of an adrenal gland of the subject, so as to treat thecondition.
 200. A method for treating a heart condition of a subject,comprising: applying, to a vagus nerve of the subject, a stimulatingcurrent which is capable of inducing action potentials in a therapeuticdirection in a first set and a second set of nerve fibers of the vagusnerve; and applying to the vagus nerve an inhibiting current which iscapable of inhibiting the induced action potentials traveling in thetherapeutic direction in the second set of nerve fibers, the nervefibers in the second set having generally larger diameters than thenerve fibers in the first set.
 201. A method according to claim 200,wherein the therapeutic direction is an efferent therapeutic directiontowards a heart of the subject, wherein applying the stimulating currentcomprises applying the stimulating current so as to induce the actionpotentials in the efferent therapeutic direction in the first and thesecond set of nerve fibers, and wherein applying the inhibiting currentcomprises applying the inhibiting current so as to inhibit the inducedaction potentials traveling in the efferent therapeutic direction in thesecond set of nerve fibers.
 202. A method according to claim 200,wherein the therapeutic direction is an afferent therapeutic directiontowards a brain of the subject, wherein applying the stimulating currentcomprises applying the stimulating current so as to induce the actionpotentials in the afferent therapeutic direction in the first and thesecond set of nerve fibers, and wherein applying the inhibiting currentcomprises applying the inhibiting current so as to inhibit the inducedaction potentials traveling in the afferent therapeutic direction in thesecond set of nerve fibers.
 203. A method according to claim 200,comprising increasing a number of action potentials traveling in thetherapeutic direction by decreasing an amplitude of the appliedinhibiting current.
 204. A method according to claim 200, wherein theheart condition includes heart failure, and wherein applying thestimulating and inhibiting currents comprises applying the stimulatingand inhibiting currents so as to treat the heart condition.
 205. Amethod according to claim 200, wherein the heart condition includescardiac arrhythmia, and wherein applying the stimulating and inhibitingcurrents comprises applying the stimulating and inhibiting currents soas to treat the heart condition.
 206. A method according to claim 200,comprising receiving an override instruction from the subject, andregulating the application of the stimulating and inhibiting currentsresponsive to the override instruction.
 207. A method according to claim200, comprising sensing a physiological state of the subject and drivinga pacemaker to apply pacing pulses to a heart of the subject responsiveto the physiological state, wherein applying the stimulating currentcomprises applying the stimulating current responsive to thephysiological state.
 208. A method according to claim 200, comprisingsensing a physiological state of the subject and driving an implantablecardioverter defibrillator to apply energy to a heart of the subjectresponsive to the physiological state, wherein applying the stimulatingcurrent comprises applying the stimulating current responsive to thephysiological state.
 209. A method according to claim 200, whereinapplying the stimulating current comprises applying the stimulatingcurrent in a series of pulses.
 210. A method according to claim 200,wherein applying the inhibiting current comprises applying theinhibiting current in a series of pulses.
 211. A method according toclaim 200, wherein applying the stimulating current comprises applyingthe stimulating current so as to regulate a heart rate of the subject.212. A method according to claim 211, wherein applying the stimulatingcurrent so as to regulate the heart rate of the subject comprisesregulating an amplitude of the stimulating current so as to regulate theheart rate of the subject.
 213. A method according to claim 200, whereinapplying the inhibiting current comprises applying the inhibitingcurrent so as to regulate a heart rate of the subject.
 214. A methodaccording to claim 213, wherein applying the inhibiting current so as toregulate the heart rate of the subject comprises regulating an amplitudeof the inhibiting current so as to regulate the heart rate of thesubject.
 215. A method according to claim 200, comprising applying tothe vagus nerve a supplementary inhibiting current, which is capable ofinhibiting induced action potentials traveling in a non-therapeuticdirection opposite the therapeutic direction in the first and secondsets of nerve fibers.
 216. A method according to claim 215, whereinapplying the supplementary inhibiting current comprises applying aprimary supplementary inhibiting current and a secondary supplementaryinhibiting current.
 217. A method according to claim 200, whereinapplying the stimulating current comprises applying the stimulatingcurrent at a stimulating location, and wherein applying the inhibitingcurrent comprises applying the inhibiting current at a primary and asecondary inhibiting location, the primary inhibiting location locatedbetween the secondary inhibiting location and the stimulating location.218. A method according to claim 217, wherein applying the inhibitingcurrent at the secondary inhibiting location comprises applying acurrent with an amplitude less than about one half an amplitude of acurrent applied at the primary inhibiting location.
 219. A methodaccording to claim 217, comprising: applying a primary supplementaryinhibiting current at a primary supplementary inhibiting location; andapplying a secondary supplementary inhibiting current at a secondarysupplementary inhibiting location, the primary supplementary inhibitinglocation located between the secondary supplementary inhibiting locationand the stimulating location, and wherein the primary and secondarysupplementary inhibiting currents are capable of inhibiting inducedaction potentials traveling in a non-therapeutic direction opposite thetherapeutic direction in the first and second sets of nerve fibers. 220.A method according to claim 219, wherein applying the secondarysupplementary inhibiting current at the secondary supplementaryinhibiting location comprises applying a current with an amplitude lessthan about one half an amplitude of a current applied at the primarysupplementary inhibiting location.
 221. A method according to claim 200,wherein applying the stimulating and inhibiting currents comprisesapplying the stimulating and inhibiting currents in respective series ofpulses.
 222. A method according to claim 221, wherein applying thestimulating and inhibiting currents comprises applying the stimulatingand inhibiting currents in respective series of about one to 20 pulses.223. A method according to claim 221, wherein applying the stimulatingand inhibiting currents comprises applying the stimulating andinhibiting currents in respective series of pulses, each pulse with aduration of between about one and three milliseconds.
 224. A methodaccording to claim 221, wherein applying the stimulating and inhibitingcurrents comprises applying the stimulating and inhibiting currents inthe respective series of pulses over a period of between about one andabout 200 milliseconds.
 225. A method according to claim 221, whereinapplying the stimulating and inhibiting currents comprises applying thestimulating and inhibiting currents in the respective series of pulsesso as to regulate a heart rate of the subject.
 226. A method accordingto claim 225, wherein applying the stimulating and inhibiting currentscomprises regulating the number of pulses in the respective series ofpulses so as to regulate the heart rate of the subject.
 227. A methodaccording to claim 225, wherein applying the stimulating and inhibitingcurrents comprises regulating a duration of each pulse so as to regulatethe heart rate of the subject.
 228. A method according to claim 225,wherein applying the stimulating and inhibiting currents comprisesvarying a length of a period of application of the respective series ofpulses so as to regulate the heart rate of the subject.
 229. A methodaccording to claim 200, comprising receiving at least one sensedparameter, and applying the stimulating and inhibiting currentsresponsive to the at least one sensed parameter.
 230. A method accordingto claim 229, comprising determining a target heart rate of the subjectresponsive to the at least one sensed parameter, wherein applying thestimulating and inhibiting currents comprises applying the stimulatingand inhibiting currents so as to adjust a heart rate of the subjecttowards the target heart rate.
 231. A method according to claim 229,wherein the at least one sensed parameter includes an indication of ablood pressure of the subject, and wherein receiving the at least onesensed parameter comprises receiving the indication of the bloodpressure.
 232. A method according to claim 229, wherein the at least onesensed parameter includes an indication of a left ventricular pressure(LVP) of the subject, and wherein receiving the at least one sensedparameter comprises receiving the indication of the LVP.
 233. A methodaccording to claim 229, wherein the at least one sensed parameterincludes an indication of a time derivative of a left ventricularpressure (LVP) of the subject, and wherein receiving the at least onesensed parameter comprises receiving the indication of the timederivative of the LVP.
 234. A method according to claim 229, wherein theat least one sensed parameter includes an indication of decreasedcardiac contractility of the subject, and wherein receiving the at leastone sensed parameter comprises receiving the indication of decreasecardiac contractility.
 235. A method according to claim 229, wherein theat least one sensed parameter includes an indication of motion of thesubject, and wherein receiving the at least one sensed parametercomprises receiving the indication of motion.
 236. A method according toclaim 229, wherein the at least one sensed parameter includes anindication of a norepinephrine concentration in the subject, and whereinreceiving the at least one sensed parameter comprises receiving theindication of the norepinephrine concentration.
 237. A method accordingto claim 229, wherein the at least one sensed parameter includes aparameter determined by impedance cardiography, and wherein receivingthe at least one sensed parameter comprises receiving the parameterdetermined by impedance cardiography.
 238. A method according to claim229, wherein the at least one sensed parameter includes an indication ofcardiac output, and wherein receiving the at least one sensed parametercomprises receiving the indication of cardiac output.
 239. A methodaccording to claim 229, wherein the at least one sensed parameterincludes an electrocardiogram (ECG) value, and wherein receiving the atleast one sensed parameter comprises receiving the ECG value.
 240. Amethod according to claim 239, wherein the at least one sensed parameterincludes an ECG value indicative of a presence of arrhythmia, andwherein receiving the at least one sensed parameter comprises receivingthe ECG value.
 241. A method according to claim 229, wherein the atleast one sensed parameter includes an indication of a heart rate of thesubject, and wherein receiving the at least one sensed parametercomprises receiving the indication of the heart rate.
 242. A methodaccording to claim 241, wherein the at least one sensed parameterincludes indications of a plurality of heart rates of the subject at arespective plurality of points in time, and wherein receiving the atleast one sensed parameter comprises receiving the indications of theplurality of heart rates and determining a measure of variability ofheart rate responsive thereto.
 243. A method according to claim 229,comprising sensing an initiation physiological parameter and atermination physiological parameter of the subject, wherein applying thestimulating and inhibiting currents comprises: applying the stimulatingand inhibiting currents to the vagus nerve after a delay; initiating thedelay responsive to the sensing of the initiation physiologicalparameter; and setting a length of the delay responsive to thetermination physiological parameter.
 244. A method according to claim243, comprising determining a target heart rate of the subjectresponsive to the at least one sensed parameter, wherein setting thelength of the delay comprises setting the length of the delay so as toadjust a heart rate of the subject towards the target heart rate.
 245. Amethod according to claim 243, wherein the termination physiologicalparameter includes an atrioventricular (AV) delay of the subject, andwherein setting the length of the delay comprises setting the length ofthe delay responsive to the AV delay.
 246. A method according to claim243, wherein the initiation physiological parameter includes a P-wave ofa cardiac cycle of the subject, and wherein initiating the delaycomprises initiating the delay responsive to the sensing of the P-wave.247. A method according to claim 243, wherein the initiationphysiological parameter includes an R-wave of a cardiac cycle of thesubject, and wherein initiating the delay comprises initiating the delayresponsive to the sensing of the R-wave.
 248. A method according toclaim 243, wherein the termination physiological parameter includes adifference in time between two features of an ECG signal recorded by theECG monitor, and wherein setting the length of the delay comprisessetting the length of the delay responsive to the difference in timebetween the two features.
 249. A method according to claim 248, whereinthe termination physiological parameter includes an R-R interval betweena sensing of an R-wave of a first cardiac cycle of the subject and asensing of an R-wave of a next cardiac cycle of the subject, and whereinsetting the length of the delay comprises setting the length of thedelay responsive to the R-R interval.
 250. A method according to claim248, wherein the termination physiological parameter includes a P-Rinterval between a sensing of a P-wave of a cardiac cycle of the subjectand a sensing of an R-wave of the cardiac cycle, and wherein setting thelength of the delay comprises setting the length of the delay responsiveto the P-R interval.
 251. A method for treating a heart condition of asubject, comprising: applying, to a vagus nerve of the subject, at astimulation location, a stimulating current which is capable of inducingaction potentials in the vagus nerve, so as to treat the subject; andapplying to the vagus nerve at a primary and a secondary location, theprimary location located between the secondary location and thestimulation location, an inhibiting current which is capable ofinhibiting action potentials in the vagus nerve.
 252. A method accordingto claim 251, wherein the primary and secondary locations are betweenabout 0.5 and about 2.0 millimeters apart from one another, and whereinapplying the inhibiting current comprises applying the inhibitingcurrent at the primary and secondary locations.
 253. A method accordingto claim 251, wherein applying the inhibiting current at the secondarylocation comprises applying the inhibiting current at the secondarylocation with an amplitude equal to between about 2 and about 5milliamps.
 254. A method according to claim 251, wherein applying theinhibiting current at the secondary location comprises applying theinhibiting current at the secondary location with an amplitude less thanabout one half an amplitude of the inhibiting current applied at theprimary location.
 255. A method according to claim 251, wherein applyingthe inhibiting current at the primary location comprises applying agenerally uniform current around a circumference of the vagus nerve atthe primary location.
 256. A method according to claim 251, whereinapplying the inhibiting current at the secondary location comprisesapplying a generally uniform current around a circumference of the vagusnerve at the secondary location.
 257. A method according to claim 251,wherein applying the stimulating current comprises applying a generallyuniform current around a circumference of the vagus nerve at thestimulation location.
 258. A method according to claim 251, whereinapplying the inhibiting current comprises applying to the vagus nervethe inhibiting current at a tertiary location, the tertiary locationlocated such that the secondary location is between the tertiarylocation and the primary location.
 259. A method according to claim 251,wherein the stimulation location is located closer than the primary andsecondary locations to a heart of the subject, with respect to actionpotentials traveling in the vagus nerve, wherein applying thestimulating current comprises applying the stimulating current at thestimulation location, and wherein applying the inhibiting currentcomprises applying the inhibiting current at the primary and secondarylocations.
 260. A method according to claim 251, wherein applying thestimulating current comprises applying the stimulating current so as toregulate a heart rate of the subject.
 261. A method according to claim251, wherein applying the inhibiting current comprises applying theinhibiting current so as to regulate a heart rate of the subject.
 262. Amethod according to claim 251, wherein the stimulation locationcomprises a plurality of discrete stimulation locations located atrespective locations around an axis of the vagus nerve, and whereinapplying the stimulating current at the stimulation location comprisesapplying the stimulating current at the plurality of discretestimulation locations, so as to selectively stimulate nerve fibers ofthe vagus nerve responsive to positions of the nerve fibers in the vagusnerve.
 263. A method according to claim 251, comprising applying to thevagus nerve at one or more supplementary locations, the supplementarylocations located so that the stimulation location is between thesupplementary locations and the primary location, an inhibiting currentwhich is capable of inhibiting action potentials propagating in thevagus nerve in a direction from the stimulation location towards thesupplementary locations.
 264. A method according to claim 251, whereinapplying the stimulating and inhibiting currents comprises applying thestimulating and inhibiting currents so as to regulate a heart rate ofthe subject.
 265. A method according to claim 251, wherein applying thestimulating current comprises applying the stimulating current in aseries of pulses.
 266. A method according to claim 251, wherein applyingthe inhibiting current comprises applying the inhibiting current in aseries of pulses.
 267. A method according to claim 251, wherein theprimary location comprises a plurality of discrete primary locationslocated at respective locations around an axis of the vagus nerve, andwherein applying the inhibiting current at the primary locationcomprises applying the inhibiting current at the plurality of discreteprimary locations.
 268. A method according to claim 267, wherein thesecondary location comprises a plurality of discrete secondary locationslocated at respective locations around an axis of the vagus nerve, andwherein applying the inhibiting current at the secondary locationcomprises applying the inhibiting current at the plurality of discretesecondary locations.
 269. A method according to claim 251, wherein thestimulation location is located closer than the primary and secondarylocations to a brain of the subject, with respect to action potentialstraveling in the vagus nerve, wherein applying the stimulating currentcomprises applying the stimulating current at the stimulation location,and wherein applying the inhibiting current comprises applying theinhibiting current at the primary and secondary locations.
 270. A methodaccording to claim 269, comprising increasing a number of actionpotentials traveling towards a heart of the subject by decreasing anamplitude of the applied inhibiting current.
 271. A method according toclaim 251, comprising receiving at least one sensed parameter, whereinapplying the stimulating and inhibiting currents comprises applying thestimulating and inhibiting currents responsive to the at least onesensed parameter.
 272. A method according to claim 271, comprisingdetermining a target heart rate of the subject responsive to the atleast one sensed parameter, and wherein applying the stimulating andinhibiting currents comprises applying the stimulating and inhibitingcurrents so as to adjust a heart rate of the subject towards the targetheart rate.
 273. A method according to claim 271, wherein the at leastone sensed parameter includes an indication of a heart rate of thesubject, and wherein receiving the at least one sensed parametercomprises receiving the indication of the heart rate.
 274. A methodaccording to claim 271, wherein the at least one sensed parameterincludes an electrocardiogram (ECG) value, and wherein receiving the atleast one sensed parameter comprises receiving the ECG value.
 275. Amethod according to claim 271, comprising sensing an initiationphysiological parameter and a termination physiological parameter of thesubject, wherein applying the stimulating and inhibiting currentscomprises: applying the stimulating and inhibiting currents to the vagusnerve after a delay; initiating the delay responsive to the sensing ofthe initiation physiological parameter; and setting a length of thedelay responsive to the termination physiological parameter.
 276. Amethod according to claim 275, comprising determining a target heartrate of the subject responsive to the at least one sensed parameter, andwherein setting the length of the delay comprises setting the length ofthe delay so as to adjust a heart rate of the subject towards the targetheart rate.
 277. A method for treating a heart condition of a subject,comprising: sensing an initiation physiological parameter and atermination physiological parameter of the subject; setting a length ofa delay period responsive to the termination physiological parameter;initiating the delay period responsive to the initiation parameter; andupon completion of the delay period, applying, to a vagus nerve of thesubject, a current which is capable of inducing action potentials thatpropagate in the vagus nerve.
 278. A method according to claim 277,wherein applying the current comprises applying the current so as toinduce action potentials that propagate in an efferent direction in thevagus nerve.
 279. A method according to claim 277, wherein applying thecurrent comprises applying the current so as to induce action potentialsthat propagate in an afferent direction in the vagus nerve.
 280. Amethod according to claim 277, wherein the heart condition includesheart failure, and wherein applying the current comprises applying thecurrent so as to treat the heart condition.
 281. A method according toclaim 277, wherein the heart condition includes cardiac arrhythmia, andwherein applying the current comprises applying the current so as totreat the heart condition.
 282. A method according to claim 277, whereinthe termination physiological parameter includes an atrioventricular(AV) delay of the subject, and wherein setting the length of the delayperiod comprises setting the length of the delay period responsive tothe AV delay.
 283. A method according to claim 277, wherein thetermination physiological parameter includes a respiration parameter ofthe subject, and wherein setting the length of the delay periodcomprises setting the length of the delay period responsive to therespiration parameter.
 284. A method according to claim 277, whereinapplying the current comprises: applying to the vagus nerve astimulating current, which is capable of inducing action potentials in atherapeutic direction in a first set and a second set of nerve fibers ofthe vagus nerve; and applying to the vagus nerve an inhibiting current,which is capable of inhibiting the induced action potentials travelingin the therapeutic direction in the second set of nerve fibers, thenerve fibers in the second set having generally larger diameters thanthe nerve fibers in the first set.
 285. A method according to claim 277,wherein applying the current comprises: applying to the vagus nerve, ata stimulation location, a stimulating current which is capable ofinducing action potentials in the vagus nerve; and applying to the vagusnerve at a primary and a secondary location, the primary locationlocated between the secondary location and the stimulation location, aninhibiting current which is capable of inhibiting action potentials inthe vagus nerve.
 286. A method according to claim 277, wherein thetermination physiological parameter includes an indication of a bloodpressure of the subject, and wherein setting the length of the delayperiod comprises setting the length of the delay period responsive tothe indication of the blood pressure.
 287. A method according to claim277, wherein sensing the initiation physiological parameter includessensing a P-wave of a cardiac cycle of the subject, and whereininitiating the delay period comprises initiating the delay periodresponsive to the sensing of the P-wave.
 288. A method according toclaim 277, wherein sensing the initiation physiological parameterincludes sensing an R-wave of a cardiac cycle of the subject, andwherein initiating the delay period comprises initiating the delayperiod responsive to the sensing of the R-wave.
 289. A method accordingto claim 277, wherein sensing the initiation physiological parameterincludes sensing a Q-wave of a cardiac cycle of the subject, and whereininitiating the delay period comprises initiating the delay periodresponsive to the sensing of the Q-wave.
 290. A method according toclaim 277, wherein sensing the initiation physiological parameterincludes sensing an S-wave of a cardiac cycle of the subject, andwherein initiating the delay period comprises initiating the delayperiod responsive to the sensing of the S-wave.
 291. A method accordingto claim 277, wherein applying the current comprises applying thecurrent so as to regulate a heart rate of the subject.
 292. A methodaccording to claim 291, wherein applying the current comprisesregulating an amplitude of the current so as to regulate the heart rateof the subject.
 293. A method according to claim 277, wherein applyingthe current comprises applying the current in a series of pulses.
 294. Amethod according to claim 293, wherein applying the current comprisesapplying the current in a series of about one to 20 pulses.
 295. Amethod according to claim 293, wherein applying the current comprisesapplying the current in a series of pulses, each pulse with a durationof between about one and three milliseconds.
 296. A method according toclaim 293, wherein applying the current comprises applying the currentin the series of pulses over a period of between about one and about 200milliseconds.
 297. A method according to claim 293, wherein applying thecurrent comprises applying the current in the series of pulses so as toregulate a heart rate of the subject.
 298. A method according to claim297, wherein applying the current comprises regulating a number ofpulses in the series of pulses so as to regulate the heart rate of thesubject.
 299. A method according to claim 297, wherein applying thecurrent comprises regulating a duration of each pulse so as to regulatethe heart rate of the subject.
 300. A method according to claim 297,wherein applying the current comprises varying a length of a period ofapplication of the series of pulses so as to regulate the heart rate ofthe subject.
 301. A method according to claim 277, comprising sensing arate-setting parameter of the subject, wherein applying the currentcomprises applying the current responsive to the rate-setting parameter,so as to regulate a heart rate of the subject.
 302. A method accordingto claim 301, wherein the rate-setting parameter includes the initiationphysiological parameter, and wherein applying the current comprisesapplying the current responsive to the initiation physiologicalparameter so as to regulate the heart rate of the subject.
 303. A methodaccording to claim 301, wherein the rate-setting parameter includes thetermination physiological parameter, and wherein applying the currentcomprises applying the current responsive to the terminationphysiological parameter so as to regulate the heart rate of the subject.304. A method according to claim 301, wherein the rate-setting parameterincludes an indication of a blood pressure of the subject, and whereinapplying the current comprises applying the current responsive to theindication of the blood pressure, so as to regulate the heart rate ofthe subject.
 305. A method according to claim 301, wherein therate-setting parameter includes an indication of a left ventricularpressure (LVP) of the subject, and wherein applying the currentcomprises applying the current responsive to the indication of the LVP,so as to regulate the heart rate of the subject.
 306. A method accordingto claim 301, wherein the rate-setting parameter includes an indicationof a time derivative of a left ventricular pressure (LVP) of thesubject, and wherein applying the current comprises applying the currentresponsive to the indication of the time derivative of the LVP, so as toregulate the heart rate of the subject.
 307. A method according to claim301, wherein the rate-setting parameter includes an indication of motionof the subject, and wherein applying the current comprises applying thecurrent responsive to the indication of motion, so as to regulate theheart rate of the subject.
 308. A method according to claim 301, whereinthe rate-setting parameter includes an indication of a norepinephrineconcentration in the subject, and wherein applying the current comprisesapplying the current responsive to the indication of the norepinephrineconcentration, so as to regulate the heart rate of the subject.
 309. Amethod according to claim 301, wherein the rate-setting parameterincludes a parameter determined by impedance cardiography, and whereinapplying the current comprises applying the current responsive to theparameter determined by impedance cardiography, so as to regulate theheart rate of the subject.
 310. A method according to claim 301, whereinthe rate-setting parameter includes an indicator of decreased cardiaccontractility, and wherein applying the current comprises applying thecurrent responsive to the indicator of decreased cardiac contractility,so as to regulate the heart rate of the subject.
 311. A method accordingto claim 301, wherein the rate-setting parameter includes an indicationof cardiac output, and wherein applying the current comprises applyingthe current responsive to the indication of cardiac output, so as toregulate the heart rate of the subject.
 312. A method according to claim301, wherein the rate-setting parameter includes an indication of aheart rate of the subject, and wherein applying the current comprisesapplying the current responsive to the indication of the heart rate, soas to regulate the heart rate of the subject.
 313. A method according toclaim 301, comprising determining a target heart rate of the subjectresponsive to the rate-setting parameter, and wherein applying thecurrent comprises applying the current so as to adjust a heart rate ofthe subject towards the target heart rate.
 314. A method according toclaim 313, wherein setting the delay period comprises setting the delayperiod so as to adjust the heart rate towards the target heart rate.315. A method according to claim 313, wherein setting the delay periodcomprises accessing one or more values stored a lookup table of delayperiods, and setting the delay period responsive to the values and tothe initiation and termination physiological parameters.
 316. A methodaccording to claim 277, comprising sensing an electrocardiogram (ECG)signal, wherein the termination physiological parameter includes adifference in time between two features of the ECG signal, and whereinsetting the length of the delay period comprises setting the length ofthe delay period responsive to the difference in time between the twofeatures.
 317. A method according to claim 316, wherein the terminationphysiological parameter includes an R-R interval between a sensing of anR-wave of a first cardiac cycle of the subject and a sensing of anR-wave of a next cardiac cycle of the subject, and wherein setting thelength of the delay period comprises setting the length of the delayperiod responsive to the R-R interval.
 318. A method according to claim317, wherein the termination physiological parameter includes an averageof R-R intervals sensed for a number of cardiac cycles, and whereinsetting the length of the delay period comprises setting the length ofthe delay period responsive to the average of the R-R intervals.
 319. Amethod according to claim 316, wherein the termination physiologicalparameter includes a P-R interval between a sensing of a P-wave of acardiac cycle of the subject and a sensing of an R-wave of the cardiaccycle, and wherein setting the length of the delay period comprisessetting the length of the delay period responsive to the P-R interval.320. A method according to claim 319, wherein the terminationphysiological parameter includes an average of P-R intervals sensed fora number of cardiac cycles, and wherein setting the length of the delayperiod comprises setting the length of the delay period responsive tothe average of the P-R intervals.
 321. A method for treating a conditionof a subject, comprising: applying, to an autonomic nerve of thesubject, a stimulating current which is capable of inducing actionpotentials in a therapeutic direction in a first set and a second set ofnerve fibers of the nerve; and applying to the nerve an inhibitingcurrent which is capable of inhibiting the induced action potentialstraveling in the therapeutic direction in the second set of nervefibers, the nerve fibers in the second set having generally largerdiameters than the nerve fibers in the first set.
 322. A method fortreating a condition of a subject, comprising: applying, to an autonomicnerve of the subject, at a stimulation location, a stimulating currentwhich is capable of inducing action potentials in the nerve, so as totreat the subject; and applying to the nerve at a primary and asecondary location, the primary location located between the secondarylocation and the stimulation location, an inhibiting current which iscapable of inhibiting action potentials in the nerve.